| 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 PR(A) isoform as compared with PR(B), 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 immunohistochemistry. 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. |
| Authors | Luisa A Helguero, Marcelo Viegas, Aroumougame Asaithamby, Gopalan Shyamala, Claudia Lanari, Alfredo A Molinolo
(Affiliation: Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.)
|
| Journal | Breast cancer research and treatment
(Breast Cancer Res Treat)
Vol. 79
Issue 3
Pg. 379-90
(Jun 2003)
ISSN: 0167-6806 Netherlands |
| PMID | 12846422
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Estrogens
- Progesterone Congeners
- Progestins
- Receptors, Progesterone
- RNA
- Medroxyprogesterone 17-Acetate
|
| Topics |
- Animals
- Blotting, Western
- Carcinoma, Ductal, Breast
(genetics, physiopathology)
- Down-Regulation
- Estrogens
(pharmacology)
- Female
- Gene Expression Regulation, Neoplastic
- Immunohistochemistry
- Mammary Neoplasms, Experimental
(genetics, physiopathology)
- Medroxyprogesterone 17-Acetate
(administration & dosage, adverse effects)
- Mice
- Mice, Inbred BALB C
- Progesterone Congeners
(administration & dosage, adverse effects)
- Progestins
(pharmacology)
- RNA
(biosynthesis)
- Receptors, Progesterone
(biosynthesis)
|
