醛酮还原酶家族1成员C3（AKR1C3）在腺癌和鳞状细胞癌中表达，但在小细胞癌中不表达。
Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma.
作者信息
Miller Valerie L, Lin Hsueh-Kung, Murugan Paari, Fan Michael, Penning Trevor M, Brame Lacy S, Yang Qing, Fung Kar-Ming
机构信息
College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
出版信息
Int J Clin Exp Pathol. 2012;5(4):278-89. Epub 2012 Apr 26.
Human aldo-keto reductase family 1 member C3 (AKR1C3) was initially identified as a critical enzyme in reducing 5α-dihydrotestosterone (5α-DHT) to 5α-androstane-3α,17β-diol (3α-diol) and oxidizing 3α-diol to androsterone. Based on these enzymatic activities, AKR1C3 was originally named type 2 3α-hydroxysteroid dehydrogenase (HSD)/type 5 17β-HSD. Additionally, AKR1C3 was demonstrated to be capable of metabolizing other steroids including estrogen and progesterone. Subsequently, AKR1C3 was shown to possess 11-ketoprostaglandin reductase activity in metabolizing prostaglandins and dihydrodiol dehydrogenase x (DDx) activity in metabolizing xenobiotics. Tissue distribution of AKR1C3 has been detected in both sex hormone-dependent organs such as the testis, breast, endometrium, and prostate as well as sex hormone-independent organs including the kidney and urothelium. Although prominent expression of AKR1C isozymes has been reported in human non-small cell lung carcinoma (NSCLC), the expression of AKR1C3 in small cell carcinoma of the lung has not been described. Also, the expression of AKR1C3 in normal lung has not been described. In this study, we demonstrated strong AKR1C3 immunoreactivity in bronchial epithelium but not in bronchial glands or alveolar pneumocytes. Strong AKR1C3 immunoreactivity was also demonstrated in columnar epithelium but only weak immunoreactivity in squamous epithelium of the gastrointestinal junction. Although AKR1C3 immunoreactivity was absent in small cell carcinoma of the lung, positive AKR1C3 immunoreactivity was extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction. AKR1C3 may serve as an adjunct marker for differentiating small cell carcinoma from NSCLC. However, roles of AKR1C3 in adenocarcinoma, squamous cell carcinoma, and small cell carcinoma pathogenesis require further studies.
人醛酮还原酶家族1成员C3（AKR1C3）最初被鉴定为一种关键酶，可将5α-二氢睾酮（5α-DHT）还原为5α-雄甾烷-3α,17β-二醇（3α-二醇），并将3α-二醇氧化为雄酮。基于这些酶活性，AKR1C3最初被命名为2型3α-羟基类固醇脱氢酶（HSD）/5型17β-羟类固醇脱氢酶。此外，已证明AKR1C3能够代谢包括雌激素和孕酮在内的其他类固醇。随后，AKR1C3在代谢前列腺素时表现出11-酮前列腺素还原酶活性，在代谢外源性物质时表现出二氢二醇脱氢酶x（DDx）活性。已在性激素依赖性器官如睾丸、乳腺、子宫内膜和前列腺以及性激素非依赖性器官包括肾脏和尿路上皮中检测到AKR1C3的组织分布。虽然已报道AKR1C同工酶在人非小细胞肺癌（NSCLC）中显著表达，但尚未描述AKR1C3在肺小细胞癌中的表达情况。此外，也未描述AKR1C3在正常肺组织中的表达情况。在本研究中，我们证明支气管上皮中存在强AKR1C3免疫反应性，而支气管腺体或肺泡上皮细胞中不存在。在柱状上皮中也证明存在强AKR1C3免疫反应性，但在胃肠交界处的鳞状上皮中仅存在弱免疫反应性。虽然肺小细胞癌中不存在AKR1C3免疫反应性，但在源自肺和胃食管交界处的腺癌和鳞状细胞癌中均广泛存在阳性AKR1C3免疫反应性。AKR1C3可作为区分小细胞癌与NSCLC的辅助标志物。然而，AKR1C3在腺癌、鳞状细胞癌和小细胞癌发病机制中的作用需要进一步研究。
Zotero 插件