A screen for genes that suppress loss of contact inhibition: Identification of ING4 as a candidate tumor suppressor gene in human cancer

Suwon Kim, Koei Chin, Joe W. Gray, J. Michael Bishop

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16251-16256
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number46
DOIs
StatePublished - Nov 16 2004

Keywords

  • Breast cancer
  • Cell transformation
  • Mutation
  • Proliferation
  • mycn

ASJC Scopus subject areas

  • General

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