Analysis of the candidate tumor suppressor ING1 gene in breast cancer.

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Down regulation of the ING1 candidate tumor suppressor promotes growth in soft agar and focus formation in vitro and tumor formation in vivo. ING1 encodes a nuclear, cell cycle-regulated protein that cooperates with p53 in the negative regulation of cell growth by transcriptionally activating the p21 gene. Overexpression of ING1 efficiently blocks cell growth and is capable of inducing apoptosis in different experimental systems. Here we present the first report of ING1mutation and expression analysis in a total of 502 cancer samples. One germline missense alteration and 3 germline silent alterations were detected in 427 primary breast cancers while marked (2-10-fold) decreases in ING1 mRNA expression were seen in 44 % of primary breast cancers and in 10 of 10 breast cancer cell lines examined. Furthermore, the majority of breast cancers (58 %) showing decreased ING1 expression had matastasized to regional lymph nodes whereas only 9 % of cancers with elevated ING1 expression, compared to adjacent normal tissues, were metastatic, Thus, ING1 mutation is very rare in breast or ovarian cancers, however, repression of ING1 expression frequently accompanies tumor development of breast cancer.