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通过实时定量逆转录-聚合酶链反应分析评估雄激素、雌激素(雌激素受体α和雌激素受体β)和孕激素受体在人前列腺癌中的表达。

Evaluation of androgen, estrogen (ER alpha and ER beta), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays.

作者信息

Latil A, Bièche I, Vidaud D, Lidereau R, Berthon P, Cussenot O, Vidaud M

机构信息

CeRePP, Université Paris VII, Evry, France.

出版信息

Cancer Res. 2001 Mar 1;61(5):1919-26.

Abstract

Steroid hormones can have profound effects on prostate tumor development making it important to define steroid receptor expression in prostate tissues. For this purpose, androgen receptor (AR) and estrogen receptor (ER alpha and ER beta) expression was quantified in 12 clinically localized and 11 hormone-refractory sporadic prostate tumors, using real-time quantitative reverse transcription-PCR assays. To gain more insight into hormone-responsiveness, estrogen-regulated progesterone receptor (PGR) and androgen-regulated prostatic acid phosphatase (PAP) mRNA levels were also quantified. There is a decrease in expression of ER beta in both clinically localized and hormone-refractory tumors relative to normal prostate tissues. Moreover, hormone-refractory tumors display a decreased expression of ER alpha and an increased expression of AR. There is a positive association between ER alpha, ER beta, and PGR expression (P < 0.0001) and a negative association between AR and the androgen-regulated gene PAP expression in hormone-refractory tumors. Taken together, these data indicate that, although increased expression of the AR gene might play a key role in endocrine treatment failure, it cannot be considered as the sole actor of this unresolved dilemma, and abnormalities in ER alpha and/or ER beta expression may also modulate the growth response of prostate cancer to hormone withdrawal. Our results also suggest that ER alpha and ER beta expression status could be used to identify advanced prostate tumor patients who may respond to antiestrogen therapy.

摘要

类固醇激素可对前列腺肿瘤的发展产生深远影响,因此明确前列腺组织中类固醇受体的表达具有重要意义。为此,采用实时定量逆转录 - 聚合酶链反应分析法,对12例临床局限性和11例激素难治性散发性前列腺肿瘤中的雄激素受体(AR)和雌激素受体(ERα和ERβ)表达进行了定量分析。为了更深入了解激素反应性,还对雌激素调节的孕激素受体(PGR)和雄激素调节的前列腺酸性磷酸酶(PAP)的mRNA水平进行了定量分析。相对于正常前列腺组织,临床局限性肿瘤和激素难治性肿瘤中ERβ的表达均降低。此外,激素难治性肿瘤显示ERα表达降低,AR表达增加。在激素难治性肿瘤中,ERα、ERβ和PGR表达之间呈正相关(P < 0.0001),AR与雄激素调节基因PAP表达之间呈负相关。综上所述,这些数据表明,虽然AR基因表达增加可能在内分泌治疗失败中起关键作用,但不能将其视为这一未解决难题的唯一因素,ERα和/或ERβ表达异常也可能调节前列腺癌对激素撤药的生长反应。我们的结果还表明,ERα和ERβ表达状态可用于识别可能对抗雌激素治疗有反应的晚期前列腺肿瘤患者。

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