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

Oncogene. 2004 Feb 12;23(6):1248-55. doi: 10.1038/sj.onc.1207245.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Mammary Glands, Animal / cytology
  • Mice
  • Mice, Transgenic
  • Mutagenesis, Site-Directed
  • Prolactin / genetics*
  • Prolactin / physiology*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Recombinant Proteins / metabolism
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Bax protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • bcl-2-Associated X Protein
  • Prolactin