title: Update on the molecular profile of the MDA-MB-453 cell line as a model for apocrine breast carcinoma studies.
abstract: Apocrine carcinoma of the breast has recently been refined through gene expression profiling. Due to various pathological studies, we compared 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 the 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 p16(INK4A) protein expression in Western blot analysis 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 the K-RAS gene (Gly13Asp GGC>GAC) was identified in the cell line, which was not observed in the six patient samples of apocrine breast carcinomas examined. Similarly, constitutive activation of the MAPK/ERK signaling pathway and 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, the MDA-MB-453 cell line shares certain features with apocrine breast carcinoma but differs from patient tissues with regard to various significant characteristics, limiting the value of this cell line as a model for human apocrine breast carcinoma investigations. In contrast to the cell line, EGFR-positive apocrine carcinomas do not harbor K-RAS gene mutations, rendering these tumors amenable to targeted therapy with EGFR inhibitors.
authors: Department of Pathology, Creighton University Medical Center, Omaha, NE, USA.
authors: Semir
authors: S
authors: Vranic
authors: Zoran
authors: Z
authors: Gatalica
authors: Zhao-Yi
authors: ZY
authors: Wang