OR30-1 Cloning, Sequencing, and Characterization of Aromatase Interacting Partner in Breast (AIPB). A New Protein Regulating Estradiol Synthesis.

Abstract Breast cancer is the most common invasive in females worldwide and accounts for 16% of all female cancers, 22.9% cancers women, 18.2% cancer-related deaths worldwide. About 80% these once established, depend on available estrogens (i.e., estradiol) to grow. The production occurs via a catalytic process governed by enzyme Aromatase. This primarily ovaries pre-menopause, while post-menopause, this peripheral tissues, including breast. In patients whose have specific hormone receptors, such as Estrogen Receptor positive (ER+), Progesterone (PR+), Human Epidermal Growth Factor 2 (HER2+), tumors can continue receiving nutrients signals grow, which provides targets therapy. Although many currently drugs breast seek suppress thus reduce estrogens, they numerous harmful side effects high rates therapy failure due development resistance. Therefore, new therapies devastating disease are needed. We observed that had increased estrogen postmenopausal leading us question cause increase. Further, complete mechanism aromatase action possibility targetable cofactors remained previously unknown. Thus, we set out identify Aromatase provide prognostic therapeutic insight into distressing disease. As an endoplasmic reticulum (ER) resident protein, purified ER fractions from separated through 1D, then each ten kDa were further analyzed Mass-spectrometry determine associated with activity. 11 mer peptide LEVVVDQPMER, cloning resulted 207 amino acid protein not present database. undiscovered colocalized ER. saw knocking down its expression siRNA wild-type cells (MCF-12A) or tumorigenic MCF-7 T47-D estradiol synthesis significantly without affecting expression. Further biochemical experiments showed interacted directly other ER-resident proteins. Additionally, our hormonally stimulated transcriptionally inhibited thus, regulates activity synthesis. termed "Aromatase Interacting Partner Breast" (AIPB). Presentation: Tuesday, June 14, 2022 9:45 a.m. - 10:00