Expression of estrogen receptor α variants (ERα46, ERα66) and c-Fos in rat mammary gland and mammary tumors

ALICIA GUTIÉRREZ, LORENA SAMBUCO, LAURA ÁLVAREZ, MARIEL NÚÑEZ, ROSA BERGOC, ELSA ZOTTA, GABRIELA MARTIN, ANDREA RANDI

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2019

Breast cancer is currently the leading cause of cancer death among women worldwide. AP-1 (c-Fos/c-Jun) is associated with proliferation and survival, while cytoplasmic c-Fos activates phospholipid synthesis in cells induced to differentiate or grow. Estrogen receptor α 46 (ERα46) is a splice variant of full-length ERα66 and it is known that it has an inhibitory role in cancer cell growth. In the present study, we investigated c-Fos localization, its relationship to AP-1, and to ERα46 and ERα66 isoforms in rat mammary gland development and carcinogenic transformation, and mammary tumors. Female rats were injected: a) saline solution (Control, CMG) or b) N-Nitroso-N-methyl urea (NMU, 50 mg/kg), and samples were taken at 60, 90, 120 and 150 days of life. In addition, we analyzed hormone-dependent (HD) and independent (HI) tumors in ovariectomized rats, and intact tumors (IT) in non-ovariectomized ones. Our results show that, in CMG, nuclear c-Fos and proliferation (PCNA)(immunohistochemistry) decreased with age (p