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Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 18, Iss 2, p 410 (2017), International Journal of Molecular Sciences; Volume 18; Issue 2; Pages: 410
- Publication Year :
- 2016
-
Abstract
- We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA) or reverse-phase protein array (RPPA), were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012). The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5), signal transducer and activator of transcription 3 (STAT3), bone morphogenetic protein 6 (BMP6), cluster of differentiation 74 (CD74), transferrin receptor (TFRC), inhibin alpha (INHA), and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88), CD74, iron exporter ferroportin (FPN), high mobility group box 1 (HMGB1), STAT3_pS727, TFRC, ferritin heavy chain (FTH), and ferritin light chain (FTL). Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer.
- Subjects :
- 0301 basic medicine
Ferroportin
lcsh:Chemistry
reverse phase protein array
0302 clinical medicine
lcsh:QH301-705.5
Spectroscopy
STAT5
ferroportin
Aged, 80 and over
biology
INHA
Iron
metabolism
breast cancer
hepcidin
transferrin receptor (TFR)
iron chelators
General Medicine
Blood Proteins
Middle Aged
Computer Science Applications
030220 oncology & carcinogenesis
Female
Breast disease
Adult
Protein Array Analysis
Transferrin receptor
Breast Neoplasms
Enzyme-Linked Immunosorbent Assay
Catalysis
Article
Inorganic Chemistry
Diagnosis, Differential
03 medical and health sciences
Young Adult
Breast cancer
Hepcidins
Hepcidin
Receptors, Transferrin
medicine
Biomarkers, Tumor
Humans
Physical and Theoretical Chemistry
Molecular Biology
Erythropoietin
Aged
Interleukin-6
Organic Chemistry
Proteins
medicine.disease
Ferritin
Ferritin light chain
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Ferritins
biology.protein
Cancer research
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 18
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....ab9221ae877e03898d2c244742c204f7