The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells.
The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells.
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发表时间：
2002-06
期刊：
影响因子：
11.2
通讯作者：
I. Kuzmin;J. Gillespie;A. Protopopov;L. Geil;K. Dreijerink;Youfeng Yang;C. Vocke;F. Duh;E. Zabar
中科院分区：
文献类型：
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作者：
I. Kuzmin;J. Gillespie;A. Protopopov;L. Geil;K. Dreijerink;Youfeng Yang;C. Vocke;F. Duh;E. Zabar
我们分析了最近发现的肿瘤抑制基因RASSF 1A在原发性前列腺癌和前列腺细胞系中的表达状态。我们发现RASSF 1A启动子在63%的原发性显微切割前列腺癌（11个样本中的7个）中完全甲基化。其余4个样本（37%）部分甲基化，可能是因为正常细胞的污染。在匹配的正常前列腺组织中未观察到启动子甲基化。在体外培养的原代正常前列腺上皮细胞和间质细胞中发现高水平的RASSF 1A转录本和RASSF 1A启动子无甲基化。RASSF 1A基因启动子在5种前列腺癌细胞系（LNCaP、PC-3、ND-1、DU-145、22 Rv 1）和1种人端粒酶催化亚单位（RC-58 T/hTERT）永生化的前列腺癌细胞系中完全沉默和甲基化。然而，在其他四种前列腺癌细胞系中没有发现RASSF 1A的沉默，这些细胞系在用人乳头瘤病毒DNA转化后适应细胞培养。在将表达RASSF 1A的构建体重新引入LNCaP前列腺癌细胞后，证实了体外细胞生长的抑制。我们的数据暗示RASSF 1A基因在人类前列腺肿瘤发生。
We analyzed expression status of the recently identified tumor suppressor geneRASSF1A in primary prostate carcinomas and in prostate cell lines. We found complete methylation of the RASSF1A promoter in 63% of primary microdissected prostate carcinomas (7 of 11 samples). The remaining 4 samples (37%) were partially methylated, possibly because of contamination with normal cells. No promoter methylation was observed in matching normal prostate tissues. High levels of RASSF1A transcript and no methylation of RASSF1A promoter were found in explanted primary normal prostate epithelial and stromal cells. Complete silencing and methylation of RASSF1A promoter was observed in five widely used prostate carcinoma cell lines, which acquired the ability to grow in culture spontaneously, including LNCaP, PC-3, ND-1, DU-145, 22Rv1, and one primary prostate carcinoma immortalized by overexpression of the human telomerase catalytic subunit (RC-58T/hTERT). However, no silencing of RASSF1A was found in four other prostate carcinoma cell lines, which were adapted for cell culture after transformation with human papillomaviral DNA. Suppression of cell growth in vitro was demonstrated after the reintroduction of RASSF1A-expressing construct into LNCaP prostate carcinoma cells. Our data implicate the RASSF1A gene in human prostate tumorigenesis.