Development of an animal model to study ovarian steroid effects on mammary carcinogenesis

SASSO V.C.; MASELLI M.E.; SANTIANO F; SEMINO S; LóPEZ FONTANA C; CARóN RW

mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigación Bioquímica

Estradiol (E) promotes cell survival in mammary cancer (MC), while in colon cancer it seems to have a protective role. We aimed to establish an animal model of MC resembling menopausal women with hormone replacement therapy which can be compared with a colon cancer model  to analyze the effects of E and progesterone(P). Sprague Dawley rats of 55 days of age were treated per os with 15mg/rat of DMBA(7,12- dimethylbenz[á]anthracene) (day0) and ovariectomized (OVX) or sham operated (SHAM) on day 30. From day 37, rats were treated (s.c) twice a week with E (60ìg/kg), P (3mg/kg), EP (at the same doses) or vehicle (VEH) for 25 weeks. At sacrifice, trunk blood and tumors were taken for hormone determinations (RIA) and histological analysis. Latency, incidence and progression of tumors were determined. E, EP and SHAM rats showed a lower latency than P and OVX. 100% of E and SHAM rats developed tumors, while the incidence for EP was 75%, for P 11% and for OVX was 0%. E increased the number of tumors per rat. Tumor growth rate was similar in all groups. E levels in E and EP rats reached physiological values. All tumors were classified as ductal carcinomas and the mitosis/apoptosis ratio tended to be higher in SHAM and EP than in E treated rats. While further molecular studies are being currently underway, we have set an appropriate model to study ovarian steroid involvement in MC to be compared to colon cancer.