Abstract
BackgroundBreast cancer is a complex disease which cannot be defined merely by clinical parameters like lymph node involvement and histological grade, or by routinely used biomarkers like estrogen receptor (ER), progesterone receptor (PGR) and epidermal growth factor receptor 2 (HER2) in diagnosis and prognosis. Breast cancer originates from the epithelial cells. Keratins (K) are cytoplasmic intermediate filament proteins of epithelial cells and changes in the expression pattern of keratins have been seen during malignant transformation in the breast. Expression of the K8/18 pair is seen in the luminal cells of the breast epithelium, and its role in prognostication of breast cancer is not well understood.Methodology/Principal FindingsIn this study, we have modulated K8 expression to understand the role of the K8/18 pair in three different breast epithelium derived cell lines: non-transformed MCF10A, transformed but poorly invasive MDA MB 468 and highly invasive MDA MB 435. The up-regulation of K8 in the invasive MDA MB 435 cell line resulted in a significant decrease in proliferation, motility, in-vitro invasion, tumor volume and lung metastasis. The down-regulation of K8 in MDA MB 468 resulted in a significant increase in transformation potential, motility and invasion in-vitro, while MCF10A did not show any changes in cell transformation assays.Conclusions/SignificanceThese results indicate the role of K8/18 in modulating invasion in breast cancer -its presence correlating with less invasive phenotype and absence correlating with highly invasive, dedifferentiated phenotype. These data may have important implications for prognostication of breast cancer.
Highlights
Breast cancer is the most prevalent form of cancer in women worldwide accounting for 23% of the total cancer cases and ranks second overall (10.9% of all cancers)
The results presented in this report show that K8/18 expression inversely correlates with motility, invasion in-vitro and metastasis invivo in breast cancer cell lines
Previous reports from both our laboratory and others have shown that an increase in K8/K18 expression in squamous cell carcinomas as well as adenocarcinomas is associated with the metastatic phenotype [32,33]
Summary
Breast cancer is the most prevalent form of cancer in women worldwide accounting for 23% of the total cancer cases and ranks second overall (10.9% of all cancers). It is the second most common cancer affecting women in India [1,2]. Breast cancers have been classified into many sub-types based on their receptor status and develop from epithelial cells in the breast tissue [3]. Expression of the K8/18 pair is seen in the luminal cells of the breast epithelium, and its role in prognostication of breast cancer is not well understood
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