ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers

Abstract

Abstract Aromatase, the rate-limiting enzyme in estrogen synthesis, is expressed in the ovaries of premenopausal, the placentas of pregnant women, and adipose tissue and skin cells in postmenopausal women, although to a lesser extent than in the ovaries. The direct mechanism of controlling breast cancer is to reduce estrogen synthesis by interfering with its production, via ovarian ablation in premenopausal women and use of aromatase inhibitors or inactivators. However, the latter results in drug resistance, making them ineffective for future treatment. In our laboratory, we identified a 22-kDa protein from human breast tissue, Aromatase Interacting Partner in Breast (AIPB), that interacts with aromatase. Western Blotting of the unaffected (nontumorigenic MCF-12A) and tumorigenic (MCF-7 ER+/PR+/Her2-) breast tissues as well as PCR amplification with the AIPB specific primers of the nontumorigenic and tumorigenic cells showed AIPB expression is maximum with the unaffected breast tissue but reduced in ER+/PR+/Her2- tumors. To confirm AIPB's regulatory role, we developed a conditional expression of AIPB by stably selecting with puromycin from MCF-7 cells and thus regulating AIPB expression under a tetracycline promoter. On addition of doxycycline followed by PCR amplification, the AIPB expression was enormously higher than the uninduced cells under identical condition. The estrogenic effect of the stable cells was reduced significantly compared to MCF-7 cells. In summary, our preliminary results suggest AIPB to be a potential biomarker with a potential for cell therapy-mediated decrease of estradiol in ER+/PR+/Her2- tumorigenic breast tissues. Presentation: No date and time listed