Loss of expression of the candidate tumor suppressor gene ZAC in breast cancer cell lines and primary tumors

Loss of chromosome 6q21-qter is the second most frequent loss of chromosoma l material in sporadic breast neoplasms suggesting the presence of at least one tumor suppressor gene on 6q, We recently isolated a cDNA encoding a ne w Zinc finger protein which we named ZAC according to its functional proper ties, namely induction of apoptosis and control of cell cycle progression. ZAC is expressed in normal mammary gland and maps to 6q24-q25, a recognized breast cancer hot spot on 6q, In the present report, we investigated the p ossible inactivation of ZAC in breast cancer cell lines and primary tumors, We detected no mutation in ZAC coding region in a panel of 45 breast tumor s with allelic imbalance of 6q24-q25, However, a survey of eight breast can cer cell lines showed a deeply reduced (three cell lines) or complete loss of (five cell lines) ZAC expression. Treatment of three of these cell lines with the methylation-interfering agent 5-azacytidine induced ZAC re-expres sion, In addition, Northern blot and RNase protection assay analysis of ZAC expression in 23 unselected primary breast tumors showed a reduced express ion in several samples. Together with its functional properties and chromos omal localization, these findings substantiate ZAC as a good candidate for the tumor suppressor gene on 6q24-q25.