Loss of heterozygosity and tumor suppressor activity of BIN1 in prostate carcinoma

The genetic events underlying the development of prostate cancer are poorly defined. c-Myc is often activated in tumors that have progressed to metast atic status, so events that promote this process may be important. Bin 1 is a nucleocytoplasmic adaptor protein with features of a tumor suppressor th at was identified through its ability to interact with and inhibit malignan t transformation by c-Myc. We investigated a role for Bin 1 loss or inactiv ation in prostate cancer because the human Bin 1 gene is located at chromos ome 2q 14 within a region that is frequently deleted in metastatic prostate cancer but where no tumor suppressor candidate has been located. A novel p olymorphic microsatellite marker located within intron 5 of the human Bin 1 gene was used to demonstrate loss of heterozygosity and coding alteration in 40% of informative cases of prostate neoplasia examined, RNA and immunoh istochemical analyses indicated that Bin 1 was expressed in most primary tu mors, even at slightly elevated levels relative to benign tissues, but that it was frequently missing or inactivated by aberrant splicing in metastati c tumors and androgen-independent tumor cell lines. Ectopic expression of B in 1 suppressed the growth of prostate cancer lines in vitro. Our findings support the candidacy of Bin 1 as the chromosome 2q prostate tumor suppress or gene. Int. J. Cancer 86:155-161, 2000. (C) 2000 Wiley-Liss, Inc.