Regulation of Estradiol Synthesis by Aromatase Interacting Partner in Breast (AIPB)
| Autor: | William E Burak, Himangshu S. Bose, Curtis E Lanier, Brian W Wheeler, Maheshinie Rajapaksha, Nicholas D Carbo, Elin M Hahn, Randy M. Whittal, Edward Perkins, Brendan Marshall, Elizabeth W Perry, Neal M Hall, Mikhail M Melomed |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.drug_class
Breast Neoplasms Biology Endoplasmic Reticulum medicine.disease_cause Aromatase Breast cancer Cell Line Tumor medicine Humans Amino Acid Sequence Breast RNA Small Interfering skin and connective tissue diseases Molecular Biology Progesterone Gene knockdown Estradiol Endoplasmic reticulum Cell Biology medicine.disease Neoplasm Proteins Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Increased risk Estrogen MCF-7 Cells biology.protein Cancer research Female RNA Interference Antibody Carcinogenesis hormones hormone substitutes and hormone antagonists Research Article |
| Zdroj: | Mol Cell Biol |
| ISSN: | 1098-5549 |
| Popis: | Estradiol is essential for the development of female sex characteristics and fertility. Postmenopausal women and breast cancer patients have high levels of estradiol. Aromatase catalyzes estradiol synthesis; however, the factors regulating aromatase activity are unknown. We identified a new 22-kDa protein, aromatase interacting partner in breast (AIPB), from the endoplasmic reticulum of human breast tissue. AIPB expression is reduced in tumorigenic breast and further reduced in triple-negative tumors. Like that of aromatase, AIPB expression is induced by nonsteroidal estrogen. We found that AIPB and aromatase interact in nontumorigenic and tumorigenic breast tissues and cells. In tumorigenic cells, conditional AIPB overexpression decreased estradiol, and blocking AIPB availability with an AIPB-binding antibody increased estradiol. Estradiol synthesis is highly increased in AIPB knockdown cells, suggesting that the newly identified AIPB protein is important for aromatase activity and a key modulator of estradiol synthesis. Thus, a change in AIPB protein expression may represent an early event in tumorigenesis and be predictive of an increased risk of developing breast cancer. |
| Databáze: | OpenAIRE |
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