Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment

Luisa A. Helguero, Marcelo Viegas, Aroumougame Asaithamby, Gopalan Shyamala, Claudia Lanari, Alfredo A. Molinolo

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Using medroxyprogesterone acetate (MPA) as a carcinogen, we were able to induce in BALB/c female mice, several progestin-dependent mammary ductal carcinomas that regress completely with estrogen or antiprogestins and are maintained by serial transplantations in syngeneic mice. Progestin-independent variants were subsequently generated or appeared spontaneously. Based on their response to estrogen or antiprogestins, we subdivided them into responsive progestin-independent (R-PI) variants which regress completely and unresponsive progestin-independent (UR-PI) carcinomas which are resistant to both families of compounds. In this study we have investigated progesterone receptor (PR) expression in six responsive progestin-dependent, six R-PI, and three UR-PI tumors. Progestin-dependent and R-PI tumors disclosed a higher expression of the PRA isoform as compared with PRB, as well as an additional band of 78 kDa that was not detected in uterine tissue; all were down-regulated by progestins. UR-PI tumors expressed lower levels of all bands in western blots, but were highly reactive by immuno-histochemistry. PR RNA expression was detected in both, UR-PI and R-PI tumors. PR binding was comparable in progestin-dependent and R-PI tumors. In the three UR-PI tumors, only 29/61 (48%) of the samples evaluated showed low binding levels, the rest were negative. This report is the first to describe in an experimental model of breast cancer the expression of PR isoforms and their distribution. Our results suggest the expression of functionally altered isoforms in a subgroup of mammary carcinomas, which may explain their lack of hormone response.

Original languageEnglish (US)
Pages (from-to)379-390
Number of pages12
JournalBreast Cancer Research and Treatment
Volume79
Issue number3
DOIs
StatePublished - Jun 1 2003

Keywords

  • Hormone dependence
  • Hormone response
  • Immunohistochemistry
  • Mammary carcinomas
  • Mice
  • Progesterone receptor isoforms
  • Western blot

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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