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Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (5), pp. e37864. Date of Electronic Publication: 2012 May 25. - Publication Year :
- 2012
-
Abstract
- Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC) (p = 0.007), while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC) (p = 0.006). Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023), ERα negativity (p = 0.001), and the HER2-driven and basal/triple-negative breast cancers (p = 0.018). Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001) and invasive breast cancer overexpressing EGFR (p = 0.019). We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120) (p<0.01). In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005). We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.
- Subjects :
- Adherens Junctions metabolism
Adult
Aged
Aged, 80 and over
Animals
Breast Neoplasms genetics
Cadherins metabolism
Carcinoma, Lobular genetics
Carcinoma, Lobular metabolism
Cell Line
ErbB Receptors metabolism
Female
Gene Expression
Humans
Mice
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
Protein Transport
Receptor, ErbB-2 deficiency
Receptors, Estrogen deficiency
Receptors, Progesterone deficiency
Transcription Factors genetics
p120 GTPase Activating Protein metabolism
Breast Neoplasms metabolism
Breast Neoplasms pathology
Carcinoma, Lobular pathology
Cell Nucleus metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22662240
- Full Text :
- https://doi.org/10.1371/journal.pone.0037864