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Update on molecular profile of the MDA-MB-453 cell line as a model for apocrine breast carcinoma studies

Apocrine carcinoma of the breast has recently been refined through the gene expression profiling and several pathology studies, which prompted us to compare the results with the MDA-MB-453 breast cancer cell line, a proposed model for apocrine breast carcinoma. The MDA-MB-453 cell line is androgen receptor positive and ‘triple-negative’ in respect to estrogen receptor-α, progesterone receptor and Her-2/neu protein expression. Cytogenetic analysis of the cell line revealed a hypertriploid clone characterized by extensive numerical and structural abnormalities including loss of the 9p.21 locus (P16-INK4a gene), also evidenced by the lack of p16INK4A protein expression in Western blot and immunocytochemistry assays. Gains of chromosomes 7 and 17 without underlying EGFR, HER-2/neu, and TOP2A gene amplification were also observed. A mutation in K- RAS gene (Gly13Asp GGC>GAC) was identified in the cell line, which was not found in six patient samples of apocrine breast carcinomas examined. Similarly, constitutive activation of the MAPK/ERK signaling pathway, deregulation of cell cycle proteins (p16-/pRb-/cyclin D1+ phenotype) with exceedingly high proliferation observed in the MDA-MB-453 cell line were not found in the tissue samples. In conclusion, MDA-MB-453 cell line shares some features with apocrine breast carcinoma but it differs from patient tissues in several important characteristics, which limits the value of this cell line as a model for human apocrine breast carcinoma research. In contrast to the cell line, EGFR-positive apocrine carcinomas do not harbor K-RAS gene mutations, which make these tumors amenable for the targeted therapy with EGFR inhibitors.

Apocrine breast carcinoma – apocrine cell line – MDA-MB-453 – androgen receptor

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