Abstract P6-14-15: Impaired Nuclear Translocation of Estrogen Receptor Alfa Could Be Associated with the Antineoplastic Effect of Iodine in Premenopausal Breast Cancer

Abstract

Abstract Several laboratories including ours have shown that iodine (I2) intake exhibits potent antiproliferative and apoptotic effects in vivo and in vitro models of mammary cancer. Molecular analysis of these effects indicates that antioxidant; cellular arrest and apoptotic pathways are involved. As the cellular mechanism that triggers these antineoplastic effects we have proposed that I2 could act in 2 possible ways, directly as antioxidant or indirectly by generating an iodinated arachidonic acid (6-iodoloctone) which exhibits apoptotic effects and is a specific ligand of proliferative peroxisome activated receptor gamma (PPARg). In previous preliminary reports, we corroborated an antiproliferative I2 effect (decreased PCNA) in premenopausal (pre-M) and an apoptotic action (triggering the Bax-Caspase pathway) in both pre-M and post menopausal (post-M) women with early stage breast cancer. In the present report we raise the casuistic and deeply in the analysis of mechanisms involved in this antineoplastic effect of I2. This study includes 22 women (average age 52.9 ± 12.6) diagnosed with early stage breast cancer (IIa and IIb). Patients were divided according to hormonal status into pre-M and post-M groups and were supplemented with I2 (5 mg daily) or placebo (vegetable dye) for2-5 weeks before surgery. Thyroid status (T3 and TSH; RIA) and iodine intake (urine, HPLC) were analyzed. In biopsies (beginning) and/or tumors (final), the level and location (cytosol or nuclear) of estrogen receptor alfa (ERα) and beta (ERb) were analyzed by immunohistochemistry. In tumors, we measured PPARg expression, invasive potential [hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF) by real time PCR] and fibrosis content (Masson's trichromic method). The results show that I2 supplementation in pre-M women is accompanied by a significant increase in the concentration of total ERα and PPARg and no change in total ERb; however, the fraction of ERα in the nucleus was significant lower, and the fibrosis content was higher (70%) than in the placebo group (40%). In contrast, I2 supplements significantly decreased HIF and VEGF expression in both pre-and post-M women. In conclusion, our data show that, in addition to the apoptotic and anti-invasive effects on mammary cancer exhibited by I2 that are independent of hormonal status, in pre-M women, I2 also acts to diminish the effects of estrogen (decreases nuclear translocation of ERα). Experiments that analyze the possible role of PPARg in these actions are in progress. We thank Dr. Jorge Alvarez-Aguirre2,3, Dr. Alonso Gallegos-Corona2, Lic. Concepción Correa-Tinajero3, Alejandro Nuñez-Nolasco2,3, Dra. Norma Uribe Uribe4, Jaime Ayala García4 and Dr. Dorothy Pless1. This work was supported by in part by PAPIIT-UNAM IN201210 and CONACyT 78955 and 85952. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-15.