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Human prolactin and its antagonist, hPRL-G129R, regulate bax and bcl-2 gene expression in human breast cancer cells and transgenic mice

Oncogene volume 23, pages 1248–1255 (2004)Cite this article

Abstract

To gain insight into the molecular mechanisms involved in human prolactin receptor antagonist (hPRL-G129R)-induced apoptosis, we used real-time reverse transcription–polymerase chain reaction to measure bax and bcl-2 gene expression in 11 human breast cancer cell lines following treatment with hPRL and hPRL-G129R. We also measured bax and bcl-2 gene expression in the mammary glands of transgenic mice expressing hPRL or hPRL-G129R. A time-course study of hPRL and antagonist treatment in T-47D cells indicated changing bax/bcl-2 mRNA ratios beginning at 24 h. We found that bax/bcl-2 mRNA ratios were significantly elevated in seven of the 11 hPRL-G129R-treated cell lines, as well as in the hPRL-G129R transgenic mice. To confirm these results, Bax and Bcl-2 proteins were analysed by Western blot methods in mammary gland tissue homogenates of transgenic mice. Bax/Bcl-2 ratios were highest in the 6-month group of hPRL-G129R transgenics, and lowest in the 6-month group of hPRL transgenics. We expanded our findings by examining the release of a downstream Bax-induced protein, cytochrome c, a hallmark protein of apoptosis, in transgenic mice. Again, cytochrome c levels were highest in the 6-month hPRL-G129R transgenic group. Thus, hPRL-G129R-induced breast cancer cell and/or mammary gland apoptosis is mediated, at least in part, through the regulation of Bax and Bcl-2 gene expression.

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Acknowledgements

We thank Dr Karl Franek for his careful review of this manuscript. This work was supported in part by the Endowment Fund of the Greenville Hospital System and grants from the US Army Medical Research Command (DAMD17-99-1-9129 and DAMD17-01-1-0207) and NIH/NCI (CA87093).

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Authors and Affiliations

  1. Department of Genetics and Biochemistry, Clemson University, Clemson, 29630, SC, USA

    Susan K Peirce

  2. Department of Biological Sciences, Clemson University, Clemson, 29630, SC, USA

    Wen Y Chen

  3. Oncology Research Institute, Greenville Hospital System, 900 West Faris Road, Greenville, 29605, SC, USA

    Wen Y Chen

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  1. Susan K Peirce
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  2. Wen Y Chen
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Correspondence to Wen Y Chen.

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Peirce, S., Chen, W. Human prolactin and its antagonist, hPRL-G129R, regulate bax and bcl-2 gene expression in human breast cancer cells and transgenic mice. Oncogene 23, 1248–1255 (2004). https://doi.org/10.1038/sj.onc.1207245

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