THU555 Stress Induced AIPB Expression In Triple Negative (ER-/PR-/Her2-) Breast Tumors Reduces Estradiol

Disclosure: M. Patrawala: None. H.S. Bose: None. In the United States, 1 in 8 women will develop invasive breast cancer in their lifetimes, and currently, more than 3.8 million individuals are survivors. Breast cancers are hormonally regulated and are categorized ER+/PR+/HER2-, ER-/PR-/HER2+, ER+/PR-/HER2-, and ER-/PR-/HER2-. In patients with Estrogen Receptor positive (Er+) and Progesterone Receptor positive (PR+), these receptors are used for targeted therapy. However, about fifteen percent of patients are diagnosed with triple-negative breast cancer. Currently, there are no molecular therapies for this cancer and only 20% of the cases respond to chemotherapy, so new prognostic markers and therapies are necessary. Aromatase, the rate limiting enzyme catalyzes testosterone to estradiol, is expressed in the ovaries of pre-menopausal women and increases 20-fold in peripheral tissues and fat bodies, like breast, in post-menopausal women contributing to tumor growth. We observed “Aromatase Interacting Partner in Breast (AIPB)” overexpression inhibits aromatase activity resulting by decreasing in estradiol. In triple-negative breast cancer, patients have a more than ten-fold decline in the expression of AIPB compared to ER+/PR+/Her2- breast tumors. Patients diagnosed with triple-negative breast cancer are profoundly stressed considering the low survival rate, which induces higher cortisol synthesis. We hypothesize the stressor will change the expression of AIPB in the tumor cells which will possibly reduce estradiol synthesis. The stress was emulated using a laboratory model in which a heat shock of 42(°) was delivered for varying periods (0,15,30,45 minutes). The model was used on engineered triple-negative tumor cells which conditionally overexpress AIPB with the addition of tetracycline. We observed MDA-MD-231 cells had a 50% reduction of estradiol from 160 ng/ml to 100 ng/ml following stress for 45 minutes. Interestingly MDA-MD-231-AIPB cells synthesized only 62 ng/ml, which is an 18.75% reduction. On addition of doxycycline, the estradiol level was further decreased to 47 ng/ml, which is about 29.4%. Western blot with a CT antibody of the MDA-MB-231-AIPB cells showed an increase in AIPB expression at the maximum level when stress was performed in combination with doxycycline. Aromatase is absent in triple-negative breast cancer, so we conclude aromatase independent action AIPB in these triple-negative tumorigenic cells plays a crucial role in estradiol synthesis. With our current data, we can suggest a model in which stimulating higher expression of AIPB in patients can provide them with better and longer lives. Presentation: Thursday, June 15, 2023