The Search for a Metastasis Suppressor Gene for Prostate Cancer on Human Chromosome 17
de la Paz, Michael G.
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The enigma of prostate cancer is determining which of the many cases of prostate cancer diagnosed will acquire metastatic ability. For this reason, effort is underway to locate metastasis suppressor genes for prostate cancer. In previous studies, Rinker-Schaeffer et al. (1994) used microcell transfer to fuse human chromosome 17 with AT6.1, a highly metastatic R-3327 dunning rat cell line, and discovered a novel metastasis suppressor region. In this SIP, the polymerase chain reaction was performed on the DNA of the metastatic revertants of four metastasis suppressing clones to determine if nonrandom deletions had occurred. Results show a nonrandom loss of the sequence tagged site D17S791 which suggests that it is the locus of the metastasis suppressor region. More detailed molecular mapping of this region in the future may provide an exact location of the metastasis suppressor gene. In addition this paper shows the results of the subcloning sequencing and BLAST search results performed using the products of differential display (which compares expressed DNA) previously performed on AT61.1 cells and the metastasis suppressed microcell hybrids, cell line AT6.1-17-4. BLAST searches revealed that several of the sequences had high identities to known cDNA sequences with unknown functions, and on the sequences appears to be a novel gene. These sequences are candidate genes for metastasis suppressor function because their functions are unknown. One sequence is a human homolog of the fission yeast cell cycle regulator gene nuc2 and two other are sequences with high identities to importin which is a homologue of the Drosophila tumor suppressor oho61. All of these sequences should be considered candidate genes responsible for metastasis suppression in human prostate cancer.