Regulation of bcl-2 gene expression in human breast cancer cells by prolactin and its antagonist, hPRL-G129R.
To gain insight into the molecular basis of human prolactin (hPRL) antagonist induced apoptosis, we compared the differential gene expression profile of four human breast cancer cell lines following treatment with hPRL and its antagonist (hPRL-G129R). Among the genes identified, the bcl-2 gene was of particular interest. We found that bcl-2 mRNA was up regulated in three of the four cell lines that were treated with hPRL. To further confirm these results, real time RT-PCR and ELISA analyses were used to detect bcl-2 mRNA and Bcl-2 protein, respectively, in 11 different breast cancer cell lines after hPRL or hPRL-G129R treatment. Our data suggests that Bcl-2 is up-regulated in response to hPRL stimulation and is competitively inhibited by hPRL-G129R in the majority of the cell lines tested. Thus, we propose that the anti-apoptotic role of hPRL in breast cancer is mediated, at least in part, through regulation of Bcl-2.
Department of Microbiology and Molecular Medicine, Clemson University, Clemson, South Carolina, SC 29630, USA.
Michael T
MT
Beck
Susan K
SK
Peirce
Wen Y
WY
Chen
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C402398:prolactin, Arg(129)-; D011388:Prolactin