A screen for genes that suppress loss of contact inhibition:: Identification of ING4 as a candidate tumor suppressor gene in human cancer
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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DOI：
10.1073/pnas.0407158101
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发表时间：
2004-11-16
影响因子：
11.1
通讯作者：
Bishop, JM
中科院分区：
文献类型：
--
作者：
Kim, S;Chin, K;Bishop, JM
我们已经设计了一种抑制原癌基因MYCN过度表达引起的接触抑制丧失的基因筛查。这一筛选的初步应用在一个有代表性的人类cDNA库中检测到了9个独特的抑制子。其中一个基因是ING4，它是一个潜在的肿瘤抑制基因，定位于人类染色体12p13。异位表达ING4可抑制MYCN或MYC诱导的接触抑制丧失，但对细胞增殖无直接影响。为了探索ING4可能是肿瘤抑制基因的可能性，我们在各种人类癌细胞系的ING4转录本中发现了失活突变。此外，我们使用比较基因组杂交检测了10%-20%的人乳腺癌细胞株和原发乳腺肿瘤中ING4基因的缺失。ING4在软琼脂中的异位表达抑制T47D人乳腺癌细胞的生长。我们认为ING4是一个很有潜力的抑癌基因。
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.