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

ING1候选肿瘤抑制因子的下调促进了体外软琼脂的生长和病灶的形成以及体内肿瘤的形成。ING1编码一种细胞核细胞周期调节蛋白，该蛋白通过转录激活p21基因与p53合作，负向调控细胞生长。在不同的实验系统中，过表达ING1能有效地阻断细胞生长并诱导细胞凋亡。本文首次报道了502例肿瘤样本中ing1的突变和表达分析。在427例原发性乳腺癌中检测到1种种系错义改变和3种种系沉默改变，而在44%的原发性乳腺癌和10个乳腺癌细胞系中观察到ING1 mRNA表达显著（2-10倍）下降。此外，大多数显示ING1表达降低的乳腺癌（58%）已经转移到局部淋巴结，而与邻近正常组织相比，ING1表达升高的癌症中只有9%发生转移。因此，ING1突变在乳腺癌或卵巢癌中非常罕见，然而，ING1表达抑制经常伴随着乳腺癌的肿瘤发展。

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.