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We aimed to examine the association between dietary isoflavone intake and the risk of breast cancer recurrence and summarize evidence on the role of dietary isoflavone intake in breast cancer prognosis. This prospective study included 592 breast cancer survivors who completed a dietary assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Of the studies published until May 31, 2023, that were searched in PUBMED and EMBASE databases, 14 studies were selected. Adjusted HRs were combined using fixed- or random-effects models. During the median follow-up of 4.3 years, 47 recurrences were identified. The HR (95% CI) for recurrence comparing the highest versus the lowest tertile of isoflavones intake was 1.29 (0.60–2.78). In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs (95% CIs) comparing the extreme categories were 0.81 (0.67–0.98) for recurrence and 0.85 (0.76–0.96) for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivors and warrants further investigation. [ABSTRACT FROM AUTHOR]

Fisetin is a flavonoid found in plants and has been reported to be effective in various human diseases. However, the effective mechanisms of ultraviolet-A (UVA)-mediated skin damage are not yet clear. In this study, we investigated the protective mechanisms of fisetin regarding UVA-induced human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) damages. Fisetin showed a cytoprotective effect against UVA irradiation and suppressed matrix metalloproteinases (MMPs), MMP-1, and MMP-3 expression. In addition, fisetin was rescued, which decreased mRNA levels of pro-inflammatory cytokines, reactive oxygen species production, and the downregulation of MAPK/AP-1 related protein and NADPH oxidase (NOX) mRNA levels. Furthermore, UVA-induced MMP-1 and MMP-3 were effectively inhibited by siRNAs to NOX 1 to 5 in HDFs and HEKs. These results indicate that fisetin suppresses UVA-induced damage through the NOX/ROS/MAPK pathway in HDFs and HEKs. [ABSTRACT FROM AUTHOR]

Simple Summary: Core needle biopsy (CNB) and fine needle aspiration (FNA) are the most commonly used non-surgical tissue sampling methods for breast cancer diagnosis. CNB has higher diagnostic accuracy and enables molecular subtype determination for neoadjuvant chemotherapy, and is more widely used than FNA. However, FNA is less invasive and provides faster results, and is still performed by many clinicians. This study was conducted to investigate the prognosis and application criteria of the two methods in real clinical practice. We found that patients who were diagnosed with breast cancer using FNA had significantly worse survival rates than those diagnosed using CNB. In the subgroup analysis, FNA showed worse survival rates in cases of highly suspicious lesions, nonpalpable tumors, or centrally located tumors. Our study may help in choosing the appropriate tissue sampling method for suspected breast cancer cases. (1) Background: Breast core needle biopsy (CNB) is preferred over fine needle aspiration (FNA) as it has higher sensitivity and specificity and enables immunohistochemical evaluation. However, breast FNA remains widely used because of its low cost, minimally invasive nature, and quick results. Studies analyzing the effects of each test on the prognoses of patients with breast cancer are scarce and controversial, and the criteria for test selection remain unknown. (2) Methods: This study included adult female patients who underwent breast cancer surgery at 102 general hospitals. The trend of breast biopsies over time was analyzed, and the prognoses of patients with breast cancer who underwent CNB and FNA were compared. (3) Results: This study included 73,644 patients who underwent FNA (n = 8027) and CNB (n = 65,617). A multivariate Cox regression analysis showed that patients diagnosed using FNA had significantly worse overall survival (OS) and breast-cancer-specific survival (BCSS) than those diagnosed using CNB. In the subgroup analysis, patients with breast imaging reporting and data system (BI-RADS) 5 lesions, palpable tumors, or centrally located tumors had significantly worse OS and BCSS with FNA than with CNB. (4) Conclusions: CNB should be performed preferentially instead of FNA in patients with BI-RADS 5 lesions and nonpalpable or centrally located tumors. [ABSTRACT FROM AUTHOR]

Aim: This study examined the associations of body mass index (BMI) and weight change with inflammatory markers among breast cancer survivors in Korea. Methods: A total of 495 women were included who had been diagnosed with primary breast cancer and survived for at least 6 months since the surgery. Information on the body weight and height of the participants was collected both at the study enrollment and diagnosis. The plasma levels of inflammatory markers were measured, including high‐sensitivity C‐reactive protein, interleukin (IL)‐6, IL‐8, tumor necrosis factor‐α, and adiponectin. A summary z‐score was calculated by summing up the z‐scores of each biomarker. The least‐square means and 95% confidence intervals (CIs) were calculated using a generalized linear model and odds ratios (ORs) and 95% CIs for the elevated levels of inflammatory markers with a multivariate logistic regression model. Results: Participants with a BMI ≥27.5 kg/m2 at the study enrollment and at diagnosis were significantly associated with elevated summary z‐scores compared to those with a BMI < 23 kg/m2; the ORs (95% CIs) were 5.42 (2.15–13.71) for current BMI and 3.66 (1.68–7.98) for BMI at diagnosis, respectively. Additionally, a weight loss > 5% since diagnosis was associated with a lower prevalence of high summary z‐scores; the OR (95% CI) was.20 (.08–.52) compared to a stable weight. Conclusions: A high BMI at diagnosis and current BMI with a greater degree were associated with unfavorable levels of inflammatory markers among breast cancer survivors. Additionally, weight loss since diagnosis was inversely associated with these markers. [ABSTRACT FROM AUTHOR]

NADPH oxidases (NOXs) are a family of membrane proteins responsible for intracellular reactive oxygen species (ROS) generation by facilitating electron transfer across biological membranes. Despite the established activation of NOXs by protein kinase C (PKC), the precise mechanism through which PKC triggers NOX activation during breast cancer invasion remains unclear. The present study aimed to investigate the role of NOX1 and NOX5 in the invasion of MCF-7 human breast cancer cells. The expression and activity of NOXs and matrix metalloprotease (MMP)-9 were assessed by reverse transcription-quantitative PCR and western blotting, and the activity of MMP-9 was monitored using zymography. Cellular invasion was assessed using the Matrigel invasion assay, whereas ROS levels were quantified using a FACSCalibur flow cytometer. The findings suggested that NOX1 and NOX5 serve crucial roles in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and invasion of MCF-7 cells. Furthermore, a connection was established between PKC and the NOX1 and 5/ROS signaling pathways in mediating TPA-induced MMP-9 expression and cellular invasion. Notably, NOX inhibitors (diphenyleneiodonium chloride and apocynin) significantly attenuated TPA-induced MMP-9 expression and invasion in MCF-7 cells. NOX1- and NOX5-specific small interfering RNAs attenuated TPA-induced MMP-9 expression and cellular invasion. In addition, knockdown of NOX1 and NOX5 suppressed TPA-induced ROS levels. Furthermore, a PKC inhibitor (GF109203X) suppressed TPA-induced intracellular ROS levels, MMP-9 expression and NOX activity in MCF-7 cells. Therefore, NOX1 and NOX5 may serve crucial roles in TPA-induced MMP-9 expression and invasion of MCF-7 breast cancer cells. Furthermore, the present study indicated that TPA-induced MMP-9 expression and cellular invasion were mediated through PKC, thus linking the NOX1 and 5/ROS signaling pathways. These findings offer novel insights into the potential mechanisms underlying their anti-invasive effects in breast cancer. [ABSTRACT FROM AUTHOR]

Background: We compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups. Methods: We compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival. Results: The ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012–1.788; p = 0.041). Conclusions: Hormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes. [ABSTRACT FROM AUTHOR]

Objective: We investigated the contribution of supplement use to total nutrient intake, the prevalence of inadequate nutrient intake and the factors associated with supplement use among breast cancer survivors. Methods: A total of 701 Korean breast cancer survivors were included. We calculated the contribution of dietary supplements to total nutrient intake and the proportion of the population below the estimated average requirements (EARs) or exceeding the tolerable upper intake levels (ULs). Stepwise logistic regression was used to identify factors associated with dietary supplement use. Results: A total of 66.5% of the survivors used dietary supplements, with multivitamins and minerals being the most commonly consumed ones. The per cent contribution of supplement to the total intake was the highest for vitamin C. 28.2%–55.4% of the non‐users consumed below the EAR of riboflavin, folate and calcium; 6.1%, 4.9% and 6.5% of the supplement users consumed above the UL of vitamins A and C, and iron, respectively. Supplement users had higher education levels or longer survival time. Conclusion: 66.5% of Korean breast cancer survivors used dietary supplements. A higher education level or prolonged survival time was associated with higher use of dietary supplements. [ABSTRACT FROM AUTHOR]

Background: There is a controversy about late-onset congestive heart failure (CHF) among breast cancer survivors. This study investigated the incidence rate and risk factors of late-onset CHF more than 2 years after the breast cancer diagnosis.Methods: A nationwide, retrospective study was conducted with the National Health Information Database. With 1:3 age- and sex-matched noncancer controls, Cox proportional hazard regression models were used to analyze the incidence and risk factors of late CHF. The cumulative incidence rate of late CHF was evaluated with a Kaplan-Meier analysis and a log-rank test.Results: A total of 91,227 cases (286,480 person-years) and 273,681 controls (884,349 person-years) were evaluated between January 2007 and December 2013. The risks of late CHF were higher in cases than controls (hazard ratio [HR], 1.396; 95% confidence interval [CI], 1.268-1.538). Younger survivors (age ≤ 50 years) showed a higher risk of late CHF than their younger counterparts (HR, 2.903; 95% CI, 2.425-3.474). Although older age was a risk factor for late CHF, older survivors (age ≥ 66 years) showed no difference in the risk of late CHF in comparison with their counterparts (HR, 0.906; 95% CI, 0.757-1.084). Anthracyclines and taxanes were risk factors for late CHF, although trastuzumab, radiation, and endocrine therapy were not.Conclusions: Young breast cancer survivors have a greater risk of late CHF than the young population without cancer. More attention should be paid to young breast cancer survivors who receive taxane- or anthracycline-based regimens over the long term. [ABSTRACT FROM AUTHOR]

Casein kinase 2 (CK2) is a serine/threonine protein kinase that has been considered to represent an important factor in mammary tumorigenesis. Increased expression of matrix metalloproteinase‑9 (MMP‑9) via nuclear factor‑κB (NF‑κB) activation has been demonstrated to promote breast cancer cell invasion. In the present study, the involvement of CK2 in protein kinase C (PKC) induced cell invasion in MCF‑7 breast cancer cells was investigated as well as the underlying molecular mechanisms. The mRNA and protein levels of MMP‑9 in MCF‑7 cells were investigated using reverse transcription‑quantitative polymerase chain reaction, western blot analyses and a zymography assay. Cell invasiveness was investigated using a Matrigel invasion assay, and it was revealed that small interfering RNA specific for CK2 suppressed PKC induced cell invasion by regulating MMP‑9 expression via activation of the p38 kinase/c‑Jun N‑terminal kinase/NF‑κB pathway. In addition, it was demonstrated that CK2 inhibitors [apigenin (20 μM), emodin (20 μM) or 2‑dimethylamino‑4,5,6,7‑tetrabromo‑1H‑benzimidazole (2 μM)] suppressed PKC induced cell invasion and MMP‑9 expression. The results of the present study suggested that CK2 is an important factor involved in the induction of MCF‑7 breast cancer cell invasion by PKC. Therefore, CK2 may represent novel candidates for therapy intended to inhibit invasion in breast cancer. [ABSTRACT FROM AUTHOR]

We identified demographic, lifestyle, and clinical factors associated with vitamin D status among breast cancer survivors. The vitamin D prediction model may be a useful surrogate of circulating 25-hydroxvitamin D (25(OH)D) concentrations when this measure was not available. We included a total of 216 Korean breast cancer survivors aged 21-79 years who had been diagnosed with stage I to III primary breast cancer and had breast cancer surgery at least 6 months before enrolment. We used linear and logistic regressions to identify determinants for the plasma 25(OH)D concentrations and vitamin D insufficiency (plasma 25(OH)D concentration < 50 nmol/L). We observed that 48.85% of breast cancer survivors had a plasma 25(OH)D concentration less than 50 nmol/L. We identified the following determinants for plasma 25(OH)D concentrations: time since diagnosis (β = -0.005 for 1 month increment), supplementary vitamin D intake (β = 0.06 for 10 µg/day increment), season of the blood draw (β = 0.35 for summer; β = 0.32 for fall; β = 0.26 for winter vs. spring), smoking status (β = 0.28 for former vs. never), use of any supplement (β = -0.35 for non-use vs. use), and the parity number (β = -0.30 for three or more vs. one) were associated with the plasma 25(OH)D concentrations. In addition to the aforementioned variables, body mass index (BMI) was associated with the prevalence of vitamin D insufficiency. We identified the determinants for the plasma 25(OH)D concentrations among Korean breast cancer survivors. Future studies are needed to investigate the role of vitamin D in the progression of breast cancer among Korean breast cancer survivors. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-γ (PPAR-γ) acts as a key factor in breast cancer metastasis. Notably, PPAR-γ can inhibit metalloproteinase (MMP), which is involved in cancer metastasis. Our previous study revealed that PPAR-γ was related to breast cancer metastasis. The present study aimed to investigate whether the PPAR-γ ligand 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) mediated suppression of cell invasion and reduced the expression of MMP-9 in breast cancer cells. The results indicated that CDDO reduced MMP-9 expression, cell migration and invasion of breast cancer cells by inhibiting TPA-induced phosphorylation of mitogen-activated protein kinases, and downregulating the activities of activator protein-1 and nuclear factor κB. Notably, knock-out of PPAR-γ by small interfering RNA in MCF-7 cells revealed that TPA-induced MMP-9 expression occurred through a PPAR-γ-independent pathway. These data indicated that the downregulatory effect of CDDO on MMP-9 expression was affected by a mechanism independent of PPAR-γ. In conclusion, the findings of the present study suggested that CDDO may act as a key agent in the regulation of breast cancer metastasis, suggesting CDDO as a new targeted therapy for breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study was performed to assess the reliability and validity of the Korean version of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Chemotherapy-induced peripheral neuropathy 20 items (EORTC QLQ-CIPN20) in patients receiving neurotoxic chemotherapy. Methods: A convenience sample of 249 Korean cancer patients, previously or currently, being treated with peripheral neurotoxic chemotherapeutic agents were asked to fill in the questionnaire. Collected data were analyzed using SPSS 21.0 and AMOS 21.0. Construct validity, known-group validity, concurrent validity, and internal consistency reliability of the Korean version of the QLQ-CIPN20 were evaluated. Results: Factor analysis confirmed 3 dimensions of CIPN: sensory, motor, and autonomic. The factor loadings of the 20 items on the 3 subscales ranged from .38 to .85. The 3 subscale-model was validated by confirmatory factor analysis (GFI=.90, AGFI=.86, RMSR=.05, NFI=.87, and CFI=.94), and concurrent validity was demonstrated with the EORTC QLQ-C30. Furthermore, the QLQ-CIPN20 established known-group validity. The Cronbach’s alpha coefficients for internal consistency of the subscales ranged from .73 to .89. Conclusion: The Korean version of the EORTC QLQ-CIPN20 showed satisfactory construct, concurrent, and known-group validity, as well as internal reliability. [ABSTRACT FROM AUTHOR]

Background: Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown.Methods: We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma.Results: Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time.Conclusions: This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients. [ABSTRACT FROM AUTHOR]

Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) ligands inhibit cell proliferation and induce apoptosis in cancer cells. Here we wished to determine whether the PPARγ ligand induces apoptosis and cell cycle arrest of the MDA-MB-231 cell, an estrogen receptor α negative breast cancer cell line. The treatment of MDA-MB-231 cell with PPARγ ligands was shown to induce inhibition of cell growth in a dose-dependent manner as determined by MTT assay. Cell cycle analysis showed a G1 arrest in MDA-MB-231 cells exposed to troglitazone. An apoptotic effect by troglitazone demonstrated that apoptotic cells elevated by 2.5-fold from the control level at 10μM, to 3.1-fold at 50μM and to 3.5-fold at 75μM. Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in pRb, cyclin D1, cyclin D2, cyclin D3, Cdk2, Cdk4 and Cdk6 expression as well as a significant increase in p21 and p27 expression. These results indicate that troglitazone causes growth inhibition, G1 arrest and apoptotic death of MDA-MB-231 cells. [Copyright &y& Elsevier]

Background: Ectopic breast tissue usually develops along the mammary ridges, and the incidence has been reported to be 2–6% of the general population. Occurrence of primary carcinoma in ectopic breast tissue is rare. Case Report: We report the case of 59-year-old woman with accessory breast carcinoma in her left axilla. Conclusion: Because an accessory areola or nipple is often missing and awareness of physicians and patients about these unsuspicious masses is lacking, clinical diagnosis of accessory breast carcinoma is frequently delayed. Therefore, a mass along the ‘milk line’ should be examined carefully, and any suspicious lesions should be evaluated. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The development and validation of guidelines for breast cancer survivors are of importance due to the increased survival rate for breast cancer. In this cross-sectional study, we aimed to examine the association between adherence to the American Cancer Society (ACS) guidelines for cancer survivors and health-related quality of life (HRQoL). A total of 618 breast cancer survivors aged 30 to 81 years who had been diagnosed with stage I to III primary breast cancer and had surgery at least a year before enrollment were included. The participants completed the 36 Item Short-Form Health Survey (SF-36) to evaluate HRQoL, and adherence scores were calculated based on the Nutrition and Physical Activity Guidelines for Cancer Survivors, which were released by the ACS. Increasing adherence scores were associated with increasing scores on the physical component summary (PCS) and the physical functioning (PF), bodily pain (BP), and vitality (VT) domains (p for trend <0.001 for PCS and PF, 0.01 for BP, and 0.02 for VT); these scores were mainly driven by the associations among survivors with stage II–III cancer. Further prospective studies are needed to evaluate whether adherence to these guidelines improves HRQoL scores among breast cancer survivors. [ABSTRACT FROM AUTHOR]

Regardless of whether the articles they examined were ultimately published, the editors would like to express their appreciation and thank the following reviewers for the time and dedication that they have shown I Cells i : those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). I Cells i was able to uphold its high standards for published papers due to the outstanding efforts of our reviewers. Thanks to the efforts of our reviewers in 2022, the median time to first decision was 16 days and the median time to publication was 42 days. [Extracted from the article]

Abstract: Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-κB), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-κB and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis. [Copyright &y& Elsevier]

Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) ligands have been identified as a potential source of therapy for human cancers. However, PPARγ ligands have a limitation for breast cancer therapy, since estrogen receptor α (ERα) negatively interferes with PPARγ signaling in breast cancer cells. Here we show that ERα inhihits PPARγ transactivity and ERα-mediated inhibition of PPARγ transactivity is blocked by tamoxifen, an estrogen receptor blocker. The activation of ERα with 17-β-estradiol blocked PPRE transactivity induced by troglitazone, a PPARγ ligand, indicating the resistance of ERα-positive breast cancer cells to troglitazone. Indeed, troglitazone inhibited the growth of ERα-negative MDA-MB-231 cells more than that of ERα-positive MCF-7 cells. Combination of troglitazone with tamoxifen led to a marked increase in growth inhibition of ERα-positive MCF-7 cells compared to either agent alone. Our data indicates that troglitazone enhances the growth inhibitory activity of tamoxifen in ERα-positive MCF-7 cells. [Copyright &y& Elsevier]

Abstract: Estrogen stimulates cell proliferation in breast cancer. The biological effects of estrogen are mediated through two intracellular receptors, estrogen receptor-α (ERα) and estrogen receptor-β (ERβ). However, the role of ERs in the proliferative action of estrogen is not well established. Recently, it has been known that ER activates phosphatidylinositol-3-OH kinase (PI3K) through binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism with subsequent formation of phosphatidylinositol-3,4,5-trisphosphate (PIP3), which is generated from phosphatidylinositol 4,5-bisphosphate via PI3K activation. The present study demonstrates that 17β-estradiol (E2) up-regulates PI3K in an ERα-dependent manner, but not ERβ, and stimulates cell growth in breast cancer cells. In order to study this phenomenon, we have treated ERα-positive MCF-7 cells and ERα-negative MDA-MB-231 cells with 10nM E2. Treatment of MCF-7 cells with E2 resulted in a marked increase in PI3K (p85) expression, which paralleled an increase in phospho-Akt (Ser-473) and PIP3 level. These observations also correlated with an increased activity to E2-induced cell proliferation. However, these effects of E2 on breast cancer cells were not observed in the MDA-MB-231 cell line, indicating that the E2-mediated up-regulation of PI3K/Akt pathway is ERα-dependent. These results suggest that estrogen activates PI3K/Akt signaling through ERα-dependent mechanism in MCF-7 cells. [Copyright &y& Elsevier]