Progesterone receptor isoforms, PR-B and PR-A, in breast cancer: correlations with clinicopathologic tumor parameters and expression of AP-1 factors

Horm Res. 2000;54(1):32-7. doi: 10.1159/000063434.

Abstract

In the present study, we used Western blot analysis to determine the expression of the progesterone receptor (PR) isoforms, PR-B and PR-A, in breast tumors (n = 53), and correlated the expression patterns of the two isoforms with the clinicopathological parameters of these tumors and with expression of the AP-1 family of transcription factors. Expression of the two PR isoforms correlated significantly with each other, indicating that the expression of the two isoforms is probably regulated in a correlated fashion. Expression of both isoforms correlated significantly with expression of the estrogen receptor (ER). Furthermore, expression of PR-B was found to correlate significantly with the absence of ErbB2/neu. For the AP-1 factors, Fra-1 expression showed an inverse correlation with PR-B expression. In contrast, expression of FosB correlated significantly with expression of both isoforms, and the association was stronger with PR-B expression. An analysis of the ratio of expression of the two isoforms showed that most of the tumors expressed PR-A levels which were equal or higher than the corresponding PR-B expression levels (together 94% of the analyzed tumors) indicating that, in mammary carcinomas, a predominance of the PR-A isoform over the PR-B isoform seems to be the case. While there was no statistically significant correlation with age, staging and histological type, expression of both isoforms correlated with a more differentiated phenotype (G1/G2 grading). However, this association was stronger for PR-B. Also, a PR-A < or = PR-B expression level was associated with G1/G2 grading, while a PR-A > PR-B expression level showed an association with a more undifferentiated phenotype (G3 grading). The expression level of the two PR isoforms might prove to be of prognostic and/or predictive value, especially since the two isoforms have been shown to be functionally different and to modulate the response of tumor cells to progestins and antiprogestins differently.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms, Male / chemistry
  • Breast Neoplasms, Male / pathology
  • Carcinoma / chemistry*
  • Carcinoma / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Protein Isoforms / analysis
  • Proto-Oncogene Proteins c-fos / analysis
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis*
  • Tumor Cells, Cultured

Substances

  • Protein Isoforms
  • Proto-Oncogene Proteins c-fos
  • Receptors, Estrogen
  • Receptors, Progesterone
  • fos-related antigen 1
  • progesterone receptor A
  • progesterone receptor B
  • Receptor, ErbB-2