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ODP540 Aromatase interacting partner in Breast (AIPB) regulates estradiol in human breast
Aromatase (estrogen synthetase) catalyzes testosterone to estradiol. It is central in reproduction, reproductive diseases, and a target for inhibitor therapy in estrogen-sensitive diseases. The level of estradiol synthesis is 20-fold or more, during menopause and in breast tumorigenesis. Unfortunate...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628869/ http://dx.doi.org/10.1210/jendso/bvac150.1795 |
Sumario: | Aromatase (estrogen synthetase) catalyzes testosterone to estradiol. It is central in reproduction, reproductive diseases, and a target for inhibitor therapy in estrogen-sensitive diseases. The level of estradiol synthesis is 20-fold or more, during menopause and in breast tumorigenesis. Unfortunately, the mechanism of increased synthesis of estradiol in these affected women is still unknown. Our laboratory has identified aromatase interacting partner (AIPB) from unaffected human breast tissue. Biochemical characterization showed that AIPB is a 22-kDa protein, present in the Endoplasmic Reticulum (ER)along with aromatase. AIPB is stimulated by estrogen but not cAMP or inactivated cycloheximide. The expression of AIPB in unaffected breast tissue and wild-type MCF-12A breast cells showed similar level of AIPB expression. Western blot with tumorigenic human breast tissues showed decrease in expression in AIPB expression in ER+/PR+/Her2- tumors. We further identified that conditional overexpression of AIPB synthesized 3.52 pg/mL of estradiol in comparison to unaffected breast tissue and wild-type MCF-12A breast cells with 9.5 pg/mL and 11.56 pg/mL, respectively. Further incubation of AIPB stable cells with estrogen stimulator, zeranol, reduced estradiol with the increase in AIPB expression confirming that aromatase activity is directly regulated by AIPB. Therefore, AIPB is crucial in understanding the pathophysiology of breast tumor development and in maintaining proper estradiol levels post-menopause and at the start of tumorigenesis. We concluded that there is potential for future advancements in the early prediction of breast cancer with the identification of AIPB expression from breast tissue. Presentation: No date and time listed |
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