Stamis Sarah A, Heath Elisabeth I, Lucas Steven, Boerner Julie, Slusher Leslie B
Department of Biology, West Chester University of Pennsylvania, West Chester, Pennsylvania, USA.
Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
Prostate. 2022 May;82(6):666-675. doi: 10.1002/pros.24310. Epub 2022 Feb 8.
In situ metabolism of ethanol by alcohol dehydrogenases (ADHs) contributes to oxidative damage of cells and DNA and has been linked to carcinogenesis in numerous epithelial tissues. The goal of this study was to determine expression patterns of ADH1 and ADH7 isozymes in normal, hyperplastic (benign prostatic hyperplasia [BPH]) and neoplastic (prostate cancer [PCa]) prostate. Furthermore, racial differences in ADH expression between African Americans and Caucasians were investigated.
ADH expression patterns were characterized by density analysis of ADH immunohistochemistry (n = 21) and real-time RT-PCR of total RNAs by laser-capture microdissection (n = 10) and whole tissue formalin-fixed paraffin embedded prostate biopsies (n = 63).
ADH protein is found in normal prostate and is primarily associated with glandular epithelium. Transcripts of ADH1B are suppressed in PCa compared to BPH (p = 0.0095). Racial differences in ADH7 transcripts exist between African American and Caucasian men. A total of 57.6% of biopsies from African American prostates have detectable ADH7 messenger RNA (mRNA) transcripts compared to the 13.3% of Caucasian prostate biopsies with detectable transcripts (p = 0.0005). This increased frequency of detection contributes to higher mean ADH7 mRNA transcript levels in African Americans (p = 0.001).
To our knowledge this study is the first to report downregulation of ADH1B in neoplastic prostate at the transcriptional level, suggesting protective regulatory functions. ADH7 transcripts were not detectable in all samples and was found in higher frequency and amount in our African American samples. Racial differences in ADH7 within the prostate is a novel finding and should be investigated further.
酒精脱氢酶（ADH）介导的乙醇原位代谢会导致细胞和DNA的氧化损伤，并与多种上皮组织的致癌作用相关。本研究的目的是确定ADH1和ADH7同工酶在正常、增生性（良性前列腺增生[BPH]）和肿瘤性（前列腺癌[PCa]）前列腺组织中的表达模式。此外，还研究了非裔美国人和白种人之间ADH表达的种族差异。
通过对ADH免疫组化进行密度分析（n = 21）以及对激光捕获显微切割获得的总RNA（n = 10）和全组织福尔马林固定石蜡包埋前列腺活检样本（n = 63）进行实时RT-PCR来表征ADH表达模式。
在正常前列腺组织中发现了ADH蛋白，且主要与腺上皮相关。与BPH相比，PCa中ADH1B的转录本受到抑制（p = 0.0095）。非裔美国男性和白种男性之间存在ADH7转录本的种族差异。非裔美国人前列腺活检样本中共有57.6%可检测到ADH7信使RNA（mRNA）转录本，而白种人前列腺活检样本中这一比例为13.3%（p = 0.0005）。这种更高的检测频率导致非裔美国人中ADH7 mRNA转录本的平均水平更高（p = 0.001）。
据我们所知，本研究首次报道了肿瘤性前列腺组织中ADH1B在转录水平的下调，提示其具有保护调节功能。并非所有样本中都能检测到ADH7转录本，且在我们的非裔美国人样本中发现其频率和含量更高。前列腺内ADH7的种族差异是一项新发现，应进一步研究。
