PROGESTERONE REGULATES GALECTIN-1 EXPRESSION IN BREAST CANCER: IMPLICATIONS FOR TUMOR-IMMUNE ESCAPE

M. SALATINO; D. CROCI; G. RABINOVICH

RIO DE JANEIRO

Congreso; 13TH INTERNATIONAL CONGRESS OF IMMUNOLOGY; 2007

ICI 2007

Progesterone regulates galectin-1 expression in breast cancer:implications for tumor-immune escape M. Salatino, D.O. Croci, and G.A. Rabinovich  Galectin-1, a carbohydrate binding protein commonly associated with immunosupresion and immune privilege, has been found to contribute to tumor progression by favoring tumor cell evasion of immune responses. Yet, the extracellular signals that regulate expression of this protein in the tumor microenvironment still remain obscure.. Progesterone, a sex steroid hormone closely related to breast cancer, has been traditionally associated to immunosupression. In the present study we evaluated the ability of progesterone to regulate galectin-1 expression in human and mouse breast cancer cells. We found that treatment with medroxiprogesterone acetate (MPA), a progesterone analogue, at a physiological doses of 10-7 M-10-8 M, induced galectin-1 expression in the hormone-dependent T47D and MCF-7 human breast cancer cells. Moreover, MPA treatment also induced galectin-1 expression in the progestin-dependent murine mammary adenocarcinoma C4HD, both in vitro and in vivo. Pretreatment of breast cancer cells with the antiprogestin RU486 (10-7 M) prevented MPA-induced galectin-1 expression, indicating that the classical progesterone receptor was involved in this regulatory effect. Time course experiments showed that galectin-1 expression started to increase only after 24 h of MPA treatment, peaked at 48 h and was maintained for as long as 72 hs. Computer assisted-sequence analysis of the gal-1 promoter region indicated the existence of a putative steroid hormone response element, clearly suggesting that progesterone directly regulates galectin-1 expression at a transcriptional level. Our results demonstrate that galectin-1 is a progesterone target gene in breast cancer, suggesting that the immunoregulatory effects of progesterone could be, at least partially, mediated by galectin-1. Further studies will reveal the physiopathologic relevane of this regulated expression in vivo.