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Mol Cell Biol ; 41(11): e0035721, 2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-34460330

RESUMEN

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.


Asunto(s)
Aromatasa/metabolismo , Neoplasias de la Mama/patología , Mama/metabolismo , Estradiol/biosíntesis , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de Neoplasias/metabolismo , Secuencia de Aminoácidos/genética , Línea Celular Tumoral , Transformación Celular Neoplásica/patología , Retículo Endoplásmico/metabolismo , Femenino , Humanos , Células MCF-7 , Progesterona/biosíntesis , Interferencia de ARN , ARN Interferente Pequeño/genética
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