Significant increase of a specific variant TSG101 transcript during the progression of cervical neoplasia
Significant increase of a specific variant TSG101 transcript during the progression of cervical neoplasia
复制标题
DOI：
10.1016/s0959-8049(99)00016-7
复制
发表时间：
1999-05-01
影响因子：
8.4
通讯作者：
Ridder, R
中科院分区：
文献类型：
--
作者：
Klaes, R;Kloor, M;Ridder, R
人类肿瘤易感基因TSG101最近在染色体位点11p15.1-15.2上被发现，该基因常受子宫颈肿瘤病变遗传改变的影响。TSG101基因的异常转录本已经在各种肿瘤实体中被报道，包括乳腺癌、卵巢癌和前列腺癌，但也在一些非肿瘤组织中。我们采用逆转录聚合酶链反应（RT-PCR）分析了TSG101在139例宫颈组织和宫颈癌细胞系临床样本中的转录情况。在所有细胞系中，在122例宫颈发育不良和癌样本中的69例（57%）和17例正常宫颈组织中的5例（29%）中观察到变异转录本。一种特定的TSG101转录本变体（Delta 154-1054）在晚期肿瘤前宫颈病变中被检测到的频率显著增加。然而，TSG101变异转录本的相对丰度似乎普遍较低，只有野生型，但在宫颈癌细胞系的Northern blot分析中没有检测到变异转录本。这些数据表明，在晚期发育不良和肿瘤中，严格的剪接控制功能逐渐丧失，或扩展了可选剪接。变异转录本的相对数量并不支持TSG101变异在宫颈癌发生中的主要功能作用。1999爱思唯尔科学有限公司版权所有。
The human tumour susceptibility gene TSG101 has recently been identified on chromosomal locus 11p15.1-15.2 which is frequently affected by genetic alterations in neoplastic lesions of the uterine cervix. Aberrant transcripts of the TSG101 gene have been reported in various tumour entities, including breast, ovarian and prostate cancers, but also in several non-neoplastic tissues. We analysed TSG101 transcription by reverse transcription-polymerase chain reaction (RT-PCR) in a total of 139 clinical samples of cervical tissues and in cervical carcinoma cell lines. Variant transcripts were observed in all cell lines, in 69 of 122 (57%) cervical dysplasia and carcinoma samples and in five of 17 (29%) normal cervical tissues. One specific variant TSG101 transcript (Delta 154-1054) was detected with a significantly increased frequency in advanced preneoplastic cervical lesions. However, the relative abundance of variant TSG101 transcripts appeared to be generally low, as only wild-type, but no variant transcripts were detectable in Northern blot analyses of cervical carcinoma cell lines. These data point to a progressive loss of stringent splice control functions or to extended alternative splicing in advanced dysplasia and neoplasia. The relative amounts of variant transcripts do not support a major functional role of TSG101 variants in cervical carcinogenesis. (C) 1999 Elsevier Science Ltd. All rights reserved.