FRI407 Identification Of AIPB Expression For Early Breast Cancer Prediction

Abstract

Abstract Disclosure: N.E. Doetch: None. H.S. Bose: None. The incidence of developing invasive breast cancer in women is about 14% during their lifetime and accounts for over 16% of all female cancers. Breast cancer is categorized based on the presence and absence of receptors including Estrogen Receptor (ER+/-), Progesterone Receptor (PR+/-), and Human Epidermal Growth Factor 2 Receptor (HER2+/-). Patients with Estrogen Receptor (ER+) and Progesterone Receptor (PR+) can participate in treatment catered to targeting both hormonally regulated receptors. Estradiol or estrogen are required and promote the growth of 80% of hormone receptor positive breast cancers which is regulated by Aromatase, a rate-limiting enzyme catalyzing the conversion of testosterone to estradiol. By decreasing estradiol synthesis, reduction in the progression of ER+/PR+ breast cancer is attainable.The expression of aromatase is increased in the ovaries of pre-menopausal women with substantial increase in peripheral and breast tissue in post-menopausal women contributing to tumor growth. “Aromatase Interacting Partner in Breast” (AIPB) has an inhibitory effect on aromatase causing a reduction in estradiol synthesis. AIPB is stimulated by detectable estrogen levels but remains unaffected by cAMP and inactivated cycloheximide. Expressed levels of AIPB were similar in unaffected breast tissue and WT MCF-12A breast cells. Western blot with tumorigenic human breast tissues showed decreased AIPB expression in ER+/PR+/HER2- tumors. We created conditional overexpression of AIPB under Tetracycline control that synthesized 3.52 pg/mL of estradiol. This was a 3-fold reduction in comparison to unaffected breast tissue and WT MCF-12A suggesting a leaky expression in tumorigenic breast cells. Findings led to hypothesis that AIPB stabilization is essential in promoting AIPB-Aromatase interaction resulting in decreased estradiol synthesis. The standard treatment for ER+/PR+ tumors, Tamoxifen, was incubated with MCF-12A cells overexpressing AIPB at varying Tamoxifen concentrations for different timed intervals and compared to untreated MCF-12A cells overexpressing AIPB and WT MCF-12A cells. Results yielded that AIPB expression in cells treated with Tamoxifen were substantially increased and no significant AIPB expression in untreated cells. MCF-12A-AIPB cells underwent incubation with Tamoxifen for 24h, soluble complex isolation, and a density gradient centrifugation. Western blotting with the CT antibody yielded one region in the density gradient fractionation in treated cells as compared to no complex formation in untreated cells. Therefore, AIPB confirmed crucial role in the pathophysiology of breast tumor development and maintenance of proper estradiol levels during post-menopause and tumorigenesis. The findings emphasize ability for future advancements in the early prediction of breast cancer with the identification of AIPB expression. Presentation: Friday, June 16, 2023