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人类前列腺癌中TSG101转录本频繁出现异常。

Frequent abnormalities of TSG101 transcripts in human prostate cancer.

作者信息

Sun Z, Pan J, Bubley G, Balk S P

机构信息

Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

出版信息

Oncogene. 1997 Dec 18;15(25):3121-5. doi: 10.1038/sj.onc.1201521.

Abstract

TSG101 has been identified as a candidate tumor suppressor gene and abnormal transcripts have been identified in a substantial fraction of breast cancers. To determine whether TSG101 expression is commonly altered in other tumors, a series of 15 primary and metastatic prostate cancers were analysed by reverse transcriptase-PCR amplification. Abnormal transcripts with extensive deletions in the coding region were found in nine of these tumors, while only the normal transcript was found in control and benign prostatic hypertrophy tissues. More than one abnormal transcript was found in four of these nine cases and distinct abnormal TSG101 transcripts were found in separate biopsies taken from one tumor. Importantly, the normal TSG101 transcript was undetectable in two metastatic prostate cancers, indicating the absence of TSG101 protein. Sequence analysis demonstrated that there were at least six distinct deletions, with four of these deletions found in more than one tumor sample. The most commonly identified deletion, from bp 153 to 1055, was identical to a deletion reported previously in breast cancer. These results demonstrate that TSG101 transcripts are frequently abnormal in prostate cancer and suggest that loss of TSG101 protein contributes to disease development or progression.

摘要

TSG101已被鉴定为一种候选肿瘤抑制基因,并且在相当一部分乳腺癌中已鉴定出异常转录本。为了确定TSG101表达在其他肿瘤中是否普遍改变,通过逆转录酶 - PCR扩增对一系列15例原发性和转移性前列腺癌进行了分析。在其中9例肿瘤中发现了编码区有广泛缺失的异常转录本,而在对照和良性前列腺增生组织中仅发现了正常转录本。在这9例中的4例中发现了一种以上的异常转录本,并且在取自同一肿瘤的不同活检组织中发现了不同的异常TSG101转录本。重要的是,在两例转移性前列腺癌中未检测到正常的TSG101转录本,这表明不存在TSG101蛋白。序列分析表明至少有六种不同的缺失,其中四种缺失在不止一个肿瘤样本中被发现。最常见的缺失是从第153位碱基对到1055位碱基对,这与先前在乳腺癌中报道的一种缺失相同。这些结果表明TSG101转录本在前列腺癌中经常异常,并提示TSG101蛋白的缺失有助于疾病的发生或进展。

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