ANX7, a candidate tumor suppressor gene for prostate cancer

The ANX7 gene is located on human chromosome 10q21, a site long hypothesize d to harbor a tumor suppressor gene(s) (TSG) associated with prostate and o ther cancers. To test whether ANX7 might be a candidate TSC, we examined th e ANX7-dependent suppression of human tumor cell growth, stage-specific ANX 7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony forma tion are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of A NX7 protein expression in human prostate tumor microarrays reveals a signif icantly higher rate of loss of ANX7 expression in metastatic and local recu rrences of hormone refractory prostate cancer as compared with primary tumo rs (P = 0.0001). Using four microsatellite markers at or near the ANX7 locu s, and laser capture microdissected tumor cells, 35% of the 20 primary pros tate tumors show LOH. The microsatellite marker closest to the ANX7 locus s howed the highest rate of LOH, including one homozygous deletion. We conclu de that the ANX7 gene exhibits many biological and genetic properties expec ted of a TSG and may play a role in prostate cancer progression.