REGULATION OF NDRG1 BY PROGESTINS/ ANTIPROGESTINS IN METASTATIC BREAST CANCER MODELS WITH DIFFERENT PROGESTERONE RECEPTOR ISOFORM RATIOS

LANARI CLAUDIA; NOVARO VIRGINIA; GIULIANELLI SEBASTIÁN; SEQUEIRA GONZALO; ALVAREZ MICHELLE; LOMBÉS MARC; RIGGIO MARINA; ABASCAL MARÍA FLORENCIA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Breast cancer (BC) is the leading cause of cancer death in women worldwide.There is compelling clinical evidence and experimental models suggesting that progesterone receptor (PR) has a role in breast cancer development and growth.The PR is a member of the steroid nuclear receptor family. Two isoforms of PR, each one with unique functions have been described, PRA (94 kDa) and PRB (115 kDa), both transcribed from a single gene.In previous studies using MPA-induced murine carcinomas and breast cancer xenografts, we demonstrated that only tumors expressing higher levels of PRA than PRB are inhibited by antiprogestins. These results were recently confirmed using tissue cultures of BC patients.NDRG1 is a metastasis suppressor gene that significantly suppressed metastasis in BC models and has been proposed as a PR-regulated gene.The effect of progestins/antiprogestins in metastatic breast cancer is still a matter of debate. The aim of this study is to develop metastatic BC models with differential PR isoform ratio and to investigate the effect of antiprogestins and progestins in tumor growth and metastasis.Progestins and antiprogestins may stimulate or inhibit respectively tumor growth/metastasis of mammary carcinomas with a high PRA/PRB ratio, and they may exert opposite effects in tumors with low PRA/PRB ratios. NDRG1 might contribute to PR-mediated effects. The influence of other hormone receptors is being investigated. Our data highlight the relevance of testing PR isoform expression before targeting PR.