Identification of Apoptosis Genes Induced by the Human Prolactin Antagonist, hPRL-G129R, in Several Breast Cancer Cell Lines

摘要

We compared the differential gene expression profile of 4 human breast cancer cell lines following treatment with hPRL or its antagonist. The Bcl-2 gene was of particular interest, and we found that this gene was upregulated in 3 of the 4 PRL-treated cell lines. Real time RT PCR analysis was used to quantitate Bax and Bcl-2 mRNA levels in 11 human breast cancer cell lines, following treatment with PRL or G129R. Bcl-2 levels increased in response to PRL treatment and Bax to G129R treatment, in a majority of cell lines tested. Findings were supported by an in vivo study using 3 age groups of PRL or G129R transgenic mice; the Bax/Bcl-2 mRNA ratio was increased in the C129R group, findings that were expanded by examining the release of a downstream Bax-induced protein, cytochrome c. These were highest in the 6 month G129R group, concomitant with the highest Bax/Bcl-2 mRNA ratio. Thus, Bax is up-regulated in response to G129R stimulation.