Understanding the role of keratins 8 and 18 in neoplastic potential of breast cancer derived cell lines.
BACKGROUND
Breast 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.


RESULTS
In 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
These 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.
Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India.
Sapna V
SV
Iyer
Prerana P
PP
Dange
Hunain
H
Alam
Sharada S
SS
Sawant
Arvind D
AD
Ingle
Anita M
AM
Borges
Neelam V
NV
Shirsat
Sorab N
SN
Dalal
Milind M
MM
Vaidya
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002999:Clone Cells; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000235:genetics / Q000378:metabolism*; D053552:Keratin-7 / Q000378:metabolism; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics; D014746:Vimentin / Q000378:metabolism
D015820:Cadherins; C488421:KRT18 protein, human; C426203:KRT8 protein, human; D053538:Keratin-18; D053552:Keratin-7; D053533:Keratin-8; D014746:Vimentin