Srivastava M, Bubendorf L, Srikantan V, Fossom L, Nolan L, Glasman M, Leighton X, Fehrle W, Pittaluga S, Raffeld M, Koivisto P, Willi N, Gasser T C, Kononen J, Sauter G, Kallioniemi O P, Srivastava S, Pollard H B
Departments of Anatomy, Physiology, and Genetics, and Institute for Molecular Medicine, Uniformed Services University School of Medicine, Bethesda, MD 20814, USA.
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4575-80. doi: 10.1073/pnas.071055798. Epub 2001 Apr 3.
The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 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 formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.
ANX7基因位于人类染色体10q21上，长期以来人们一直假设该位点存在与前列腺癌及其他癌症相关的肿瘤抑制基因（TSG）。为了检测ANX7是否可能是一个候选肿瘤抑制基因，我们研究了ANX7对人类肿瘤细胞生长的依赖性抑制作用、在前列腺组织微阵列上301个前列腺标本中ANX7的阶段特异性表达，以及ANX7基因座处或其附近微卫星标记的杂合性缺失（LOH）。在此我们报告，当野生型ANX7基因转染到两种前列腺肿瘤细胞系LNCaP和DU145中时，人类肿瘤细胞的增殖和集落形成明显减少。同样，对人类前列腺肿瘤微阵列中ANX7蛋白表达的分析显示，与原发性肿瘤相比，激素难治性前列腺癌转移和局部复发中ANX7表达缺失的发生率显著更高（P = 0.0001）。使用ANX7基因座处或其附近的四个微卫星标记以及激光捕获显微切割的肿瘤细胞，20个原发性前列腺肿瘤中有35%显示杂合性缺失。最接近ANX7基因座的微卫星标记显示出最高的杂合性缺失率，包括一个纯合缺失。我们得出结论，ANX7基因表现出许多肿瘤抑制基因所预期的生物学和遗传学特性，可能在前列腺癌进展中发挥作用。
