The ratio of progesterone receptor isoforms predicts progestin and antiprogestin response: Interaction of PR with AIB1 or SMRT

MARINA RIGGIO, SEBASTIÁN GIULIANELLI, VICTORIA WARGON, VIRGINIA NOVARO, CLAUDIA LANARI

Washington

Congreso; Annual Meeting of the American Association of Cancer Research; 2013

AACR

We havepreviously demonstrated in a mouse model of breast cancer that mammary carcinomaswhich are responsive to the antiprogestin mifepristone (MFP) express higherlevels of isoform A of progesterone receptor (PRA) than isoform B (PRB). PRB ispredominant in tumors with constitutive or acquired resistance to MFP, indicatingthat the PR isoform ratio might predict antiprogestin responsiveness.The aim of thisstudy was to evaluate the effect of MFP and of medroxyprogesterone acetate (MPA)on the growth of human breast cancer xenografts showing different ratios of PRisoforms.We chose IBH-6cells since they express hormone receptors and they give rise to tumorxenografts without the need of exogenous hormone supply. IBH-6 tumors express higherlevels of PRB than PRA and they are not inhibited by antiprogestin treatment.We stablytransfected these cells with PRA, PRB or empty vector and sc inoculated 106transfected cells into the right flank of female nude (nu/nu) mice. When tumors reached a size of 9 mm2,animals were treated sc with MFP (10 mg/kg/day), MPA (20 mg depot) or vehicle.Interestingly,only tumors showing higher levels of PRA than PRB were inhibited with MFPtreatment (p