of nkx3 1 to that of a mutated derivative nkx3 1 l s containing a substitution of a conserved residue in the homeodomain the resulting mutant protein is stable and localizes to the nucleus as does wild type nkx3 1 but is inactive in dna binding and transcription assays p sciavolino and c a s unpublished observations we examined the consequences of nkx3 1 misexpression using human pc3 and rodent at6 prostate carcinoma cell lines that do not express endogenous nkx3 1 fig1 a 25 26 these results showed that misexpression of nkx3 1 but not nkx3 1 1 l s resulted in a 73 reduction in cellular proliferation in at6 cells and a 59 reduction in pc3 cells fig1 b we also found that misexpression of nkx3 1 resulted in 58 reduction in anchorage independent growth of at6 cells p lt 0 05 fig1 c d moreover nkx3 1 expressing at6 and pc3 cells displayed decreased tumor growth in nude mice of 47 or 59 respectively p lt 0 01 fig1 e similar results were obtained in all assays using a human nkx3 1 retrovirus as well as stable tetracycline inducible cell lines expressing mouse or human nkx3 1 data not shown these tumor suppressor activities of nkx3 1 in cell culture and nude mice are consistent with the observation that nkx3 1 mutant mice display increased proliferation of prostatic epithelium 9 despite these activities of nkx3 1 and its localization to 8p21 previous studies have failed to detect mutational inactivation of the coding sequence in human prostate carcinoma 7 we have confirmed these findings by.