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Localization of prostate cancer metastasis-suppressor activity on human chromosome 17
M A Chekmareva1, C M Hollowell, R C Smith
1Department of Surgery, University of Chicago, Illinois 60637, USA.
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.