Sarkar F H, Sakr W, Li Y W, Macoska J, Ball D E, Crissman J D
Department of Pathology, Wayne State University, School of Medicine, Detroit, MI 48201.
Prostate. 1992;21(2):145-52. doi: 10.1002/pros.2990210207.
The retinoblastoma tumor suppressor gene (RB gene) has been reported to be deleted and/or modified in a number of human cancers, indicating that dysfunction of this tumor suppressor gene is perhaps critical in the development of many human tumors. In addition to deletion of one copy and/or mutational inactivation of the RB gene, this gene has also been reported to be altered by a small deletion in the promoter sequence in one case of small cell mixed adenocarcinoma of the prostate. A deletion of 105 nucleotides of the RB gene in exon 21, leading to an aberrant short-sized mRNA transcript, has also been reported in one cell line (DU 145) derived from brain metastasis of prostatic adenocarcinoma. We have analyzed tissues from 10 prostate specimens (3 hyperplastic and 7 neoplastic) and one prostate cancer cell line (DU 145) for the presence of short-sized mRNA transcript (exon 21 alterations) by polymerase chain reaction (PCR) using total RNA extracted from frozen tumors and the cell line. None of the prostate tissue showed any evidence of aberrant short-sized mRNA, although it was confirmed in the DU 145 cell line. Simultaneously, we have used DNA-PCR to investigate RB promoter deletion in 23 adenocarcinomas and one small cell carcinoma of the prostate. We also failed to demonstrate any indication of RB promoter deletion at the DNA level in adenocarcinomas. The single case of small cell carcinoma failed to show evidence of any aberration in RB promoter. We therefore conclude that neither RB promoter alterations nor the exon 21 deletion are associated with typical prostate adenocarcinoma.
据报道,视网膜母细胞瘤抑癌基因(RB基因)在多种人类癌症中发生缺失和/或改变,这表明该抑癌基因功能障碍可能在许多人类肿瘤的发生发展中起关键作用。除了RB基因的一个拷贝缺失和/或突变失活外,在一例前列腺小细胞混合腺癌中,还报道该基因因启动子序列的小片段缺失而发生改变。在一株源自前列腺腺癌脑转移的细胞系(DU 145)中,也报道了RB基因第21外显子缺失105个核苷酸,导致异常短尺寸mRNA转录本的出现。我们使用从冷冻肿瘤和细胞系中提取的总RNA,通过聚合酶链反应(PCR)分析了10份前列腺标本(3份增生性和7份肿瘤性)的组织以及一株前列腺癌细胞系(DU 145),以检测短尺寸mRNA转录本(第21外显子改变)的存在。尽管在DU 145细胞系中得到证实,但前列腺组织均未显示出任何异常短尺寸mRNA的证据。同时,我们使用DNA-PCR研究了23例前列腺腺癌和1例前列腺小细胞癌中的RB启动子缺失情况。我们也未能在腺癌的DNA水平上证明有任何RB启动子缺失的迹象。该例小细胞癌未显示出RB启动子有任何异常的证据。因此,我们得出结论,RB启动子改变和第21外显子缺失均与典型前列腺腺癌无关。