SUN-487 Stress-Induced AIPB Expression Reduces Estradiol Synthesis

Abstract D.M. Pham: None. M. Patrawala: None. H.S. Bose: None. Breast cancer is derived from malignant genetic mutations due to uncontrolled cell division. In 2020, 2.3 million new cases of breast cancer were diagnosed, affecting one in eight women. Aromatase enzyme catalyzes the conversion of androgens into estrogen in the endoplasmic reticulum. Breast cancers are influenced by hormone factors, which are nurtured by the presence or absence of Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor (HER2). Roughly ten to fifteen percent of cases have no receptor expression with no molecular-based therapies available for treatment. Development of novel prognostic markers and therapeutic interventions is needed. Aromatase-Interacting Partner in Breast (AIPB), a novel 22 kDa protein present in the breast, is not transcriptionally activated or acutely regulated. We have observed the expression of AIPB is directly related to estradiol synthesis. Patients with breast cancer develop physiological stress for themselves, especially with mothers having younger children. We hypothesize that AIPB expression will increase with stress and will be related to changes in estradiol. We stressed the cells with heat shock for 15, 25, and 35 minutes, and measured AIPB expression by Western Blot and activity by estradiol synthesis. We found that triple-negative breast cancer cells, MDA-MB-231, experienced a 50% decrease in estradiol levels, declining from 160 ng/ml to 100 ng/ml after stress for 45 minutes. Intriguingly, MDA-MB-231 cells conditionally expressing AIPB decreased estradiol to 62 ng/ml, representing an 18.75% reduction. Addition of doxycycline to the conditionally expressed cells resulted in estradiol to 47 ng/ml or 29.4%. Western Blot shows that AIPB expression is increased in tumorigenic cells under stress and AIPB expression is greatest in cells undergoing prolonged stress. We conclude that AIPB expression is directly correlated to stress, and estradiol activity is inversely correlated to stress. These findings enhance the understanding of the inhibitory role of AIPB on estradiol and serve as a foundation for future research on potential curative therapies for triple-negative breast cancer. Sunday, June 2, 2024