前列腺癌转移抑制活性在人类17号染色体上的定位

Localization of prostate cancer metastasis-suppressor activity on human chromosome 17.

作者信息

Chekmareva M A, Hollowell C M, Smith R C, Davis E M, LeBeau M M, Rinker-Schaeffer C W

机构信息

Department of Surgery, University of Chicago, Illinois 60637, USA.

出版信息

Prostate. 1997 Dec 1;33(4):271-80. doi: 10.1002/(sici)1097-0045(19971201)33:4<271::aid-pros8>3.0.co;2-k.

DOI:10.1002/(sici)1097-0045(19971201)33:4<271::aid-pros8>3.0.co;2-k

PMID:9397200

Abstract

BACKGROUND

Prostate cancer is the most commonly diagnosed malignancy in American men. Currently, it is difficult to accurately predict the clinical course of histologically localized prostatic cancer in the individual patient. Identification of markers for metastatic potential of prostate cancer may improve the diagnosis and treatment of this disease. We have previously demonstrated that human chromosome 17 (17pter-q23) suppresses the metastatic ability of AT6.1 rat prostatic cancer cells. In this study we report on the further localization of the metastasis suppressor activity encoded by human chromosome 17.

METHODS

A series of AT6.1-17 microcell hybrids was constructed using microcell-mediated chromosomal transfer of human chromosome 17 into highly metastatic AT6.1 cells. Hybrids which had spontaneously deleted regions of chromosome 17 were analyzed by PCR for the presence of 32 sequence-tagged sites (STS) markers as well as the prostate cancer tumor-suppressor loci reported on 17q. In addition, we examined a number of candidate genes and markers that previously have been mapped to chromosome 17. The in vivo metastatic potential of these AT6.1-17 deletion hybrids was determined.

RESULTS

We have localized metastasis-suppressor activity to a approximately 70-centiMorgan (cM) portion of chromosome 17, consisting of three distinct regions of 30 cM (D17S952-->D17S805), 6 cM (D17S930-->D17S797), and 34 cM (D17S944-->D17S784). Three of the four markers on 17p13, including HIC1 and TP53, and 12 of the 13 markers in 17q21-23, including BRCA1 (D17S855) and NM23 (NME1), were not retained in the conserved approximately 70-cM metastasis-suppressor region.

CONCLUSIONS

These results support a role for a novel metastasis-suppressor gene(s) or a novel metastasis-suppressor function on chromosome 17. Complementary candidate gene and positional cloning approaches are being used to identify the gene(s) within the approximately 70-cM conserved region responsible for metastasis suppression.

摘要

背景

前列腺癌是美国男性中最常被诊断出的恶性肿瘤。目前，很难准确预测个体患者组织学上局限的前列腺癌的临床进程。鉴定前列腺癌转移潜能的标志物可能会改善这种疾病的诊断和治疗。我们之前已经证明，人类染色体17（17pter-q23）可抑制AT6.1大鼠前列腺癌细胞的转移能力。在本研究中，我们报告了人类染色体17编码的转移抑制活性的进一步定位。

方法

使用微细胞介导的染色体转移技术，将人类染色体17导入高转移性的AT6.1细胞中，构建了一系列AT6.1-17微细胞杂种。通过PCR分析自发缺失染色体17区域的杂种，检测32个序列标签位点（STS）标记以及17q上报道的前列腺癌肿瘤抑制基因座的存在情况。此外，我们还检测了一些先前已定位到染色体17上的候选基因和标记。测定了这些AT6.1-17缺失杂种的体内转移潜能。

结果

我们已将转移抑制活性定位到染色体17上约70厘摩（cM）的区域，该区域由三个不同的区域组成，分别为30 cM（D17S952→D17S805）、6 cM（D17S930→D17S797）和34 cM（D17S944→D17S784）。17p13上的四个标记中的三个，包括HIC1和TP53，以及17q21-23中的13个标记中的12个，包括BRCA1（D17S855）和NM23（NME1），未保留在保守的约70-cM转移抑制区域中。