Genetic instability of RBM5/LUCA-15/H37 in MCF-7 breast carcinoma sublines may affect susceptibility to apoptosis.

The MCF-7 human breast carcinoma cell line is widely used as a model system by breast cancer researchers and cell biologists investigating apoptosis. Since its establishment 30 years ago, from a patient with metastatic breast cancer, the original MCF-7 cell population has undergone genetic drift to such an extent that numerous genetically diverse sublines now exist. For instance, it has been reported that MCF-7 cells have lost the region 3p21.3, to which the apoptosis regulatory protein and putative tumour suppressor LUCA-15 (also called RBM5 and H37) maps; however, LUCA-15 has been cloned from MCF-7 cells, and LUCA-15 expression analyses have been conducted using MCF-7 cells. To address this discrepancy, we characterized three MCF-7 sublines by Western blot, RT-PCR and finally genomic PCR analysis, and determined that one of the three had lost the LUCA-15 gene. Interestingly, loss of LUCA-15 was positively correlated with decreased susceptibility to the death-inducing ligand TNF-alpha. Subsequent overexpression of exogenous LUCA-15 was shown to enhance TNF-alpha-mediated apoptosis, suggesting that LUCA-15 may play a role in regulating the susceptibility of breast cancer cells to drug-induced apoptosis. These results not only reinforce the necessity of MCF-7 subline characterization, but provide the first evidence of an apoptotic modulatory role for LUCA-15 in a non-T cell line.