ANX7, a candidate tumor suppressor gene for prostate cancer

^*Departments of Anatomy, Physiology, and Genetics, and Institute for Molecular Medicine, and ^¶Center for Prostate Disease Research, and Department of Surgery, Uniformed Services University School of Medicine, Bethesda, MD 20814; ^‡Section on Molecular Genetics, Cancer Genetics Branch, National Human Genome Research Institute, and ^‖Laboratory of Pathology, Hematopathology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; ^**Laboratory of Cancer Genetics, Tampere University Hospital, FIN-33520 Tampere, Finland; and ^§Institute for Pathology and ^‡‡Urologic Clinics, University of Basel, CH-4031 Basel, Switzerland

Communicated by Bernhard Witkop, National Institutes of Health, Bethesda, MD (received for review December 29, 2000)

Abstract

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.

Footnotes

↵ † To whom reprint requests should be addressed at: Departments of Anatomy, Physiology, and Genetics, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD 20814. E-mail: msrivastava{at}usuhs.mil or hpollard{at}usuhs.mil.
↵ †† Nomenclature: Italics are used to denote genes, while roman text is for cognate proteins. Uppercase letters are for human genes (e.g., ANX7); uppercase first letters denote mouse genes (e.g., Anx7); lowercase letters denote a gene from other species (e.g., anx7).
Abbreviations:

LOH,

loss of heterozygosity;

TSG,

tumor suppressor gene;

CaP,

carcinoma of the prostate