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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer.
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A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer.

机译：筛选抑制接触抑制丧失的基因：鉴定ING4作为人类癌症中的候选肿瘤抑制基因。

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摘要

We have devised a screen for genes that suppress the loss of contact inhibition elicited by overexpression of the protooncogene MYCN. The initial application of this screen detected nine distinctive suppressors within a representative human cDNA library. One of these genes was ING4, a potential tumor suppressor gene that maps to human chromosome 12p13. Ectopic expression of ING4 suppressed the loss of contact inhibition elicited by either MYCN or MYC but had no direct effect on cellular proliferation. Pursuing the possibility that ING4 might be a tumor suppressor gene, we found inactivating mutations in ING4 transcripts from various human cancer cell lines. In addition, we used comparative genomic hybridization to detect deletion of the ING4 locus in 10-20% of human breast cancer cell lines and primary breast tumors. Ectopic expression of ING4 attenuated the growth of T47D human breast cancer cells in soft agar. We conclude that ING4 is a strong candidate as a tumor suppressor gene.
机译：我们设计了一种筛选基因的筛选方法，该基因可抑制原癌基因MYCN的过表达引起的接触抑制作用的丧失。该筛选的最初应用在代表性的人类cDNA文库中检测到九种独特的抑制子。这些基因之一是ING4，这是一种潜在的抑癌基因，可映射到人类12p13染色体。 ING4的异位表达抑制了MYCN或MYC引起的接触抑制丧失，但对细胞增殖没有直接影响。为寻找ING4可能是抑癌基因的可能性，我们发现了来自各种人类癌细胞系的ING4转录本中的失活突变。此外，我们使用比较基因组杂交技术检测了10％至20％的人乳腺癌细胞系和原发性乳腺肿瘤中ING4基因座的缺失。 ING4的异位表达减弱了软琼脂中T47D人乳腺癌细胞的生长。我们得出结论，ING4作为肿瘤抑制基因是很强的候选者。

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