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

乳腺癌候选抑癌基因 ING1 的分析。

• 批准号: 12671167
• 负责人: TOYAMA Tatsuya
• 金额: $ 2.11万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671167/
• 关键词: ING1; tumor suppressor gene; breast cancer; ING1遺伝子; 分子生物学

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.

ING 1候选肿瘤抑制因子的下调促进软琼脂中的生长和体外病灶形成以及体内肿瘤形成。ING 1编码一种核细胞周期调节蛋白，通过转录激活p21基因与p53合作负调控细胞生长。ING 1的过表达有效地阻断细胞生长，并且能够在不同的实验系统中诱导细胞凋亡。本文首次报道了502例肿瘤组织中ING 1基因的突变和表达分析。在427例原发性乳腺癌中检测到1个生殖系错义改变和3个生殖系沉默改变，而在44%的原发性乳腺癌和10个乳腺癌细胞系中观察到ING 1 mRNA表达显著（2-10倍）降低。此外，显示ING 1表达降低的大多数乳腺癌（58%）已经转移到区域淋巴结，而与邻近正常组织相比，ING 1表达升高的癌症仅9%是转移性的。因此，ING 1突变在乳腺癌或卵巢癌中非常罕见，然而，ING 1表达的抑制经常伴随乳腺癌的肿瘤发展。