Expression of the wild-type insulin-like growth factor II receptor gene suppresses growth and causes death in colorectal carcinoma cells

Rhonda F. Souza, Suna Wang, Manjusha Thakar, Kara N. Smolinski, Jing Yin, Tong Tong Zou, Dehe Kong, John M. Abraham, Jeffrey A. Toretsky, Stephen J. Meltzer

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The insulin-like growth factor II receptor (IGFIIR) has been implicated as a tumor suppressor gene in human malignancy. Frequent mutation, loss of heterozygosity, and microsatellite instability (MSI) directly affecting the IGFIIR gene have been reported in several primary human tumor types. However, to our knowledge, dynamic functional evidence of a growth-suppressive role for IGFIIR has not yet been provided. We identified one MSI-positive colorectal carcinoma cell line, SW48, with monoallelic mutation in IGFIIR identical to that seen in primary colorectal carcinomas. A zinc-inducible construct containing the wild-type IGFIIR cDNA was stably transfected into SW48 cells. Growth rate and apoptosis were compared between zinc-treated, untreated, and untransfected cells. A twofold increase in IGFIIR protein expression was detected after zinc treatment in discrete clonal isolates of transfected SW48 cells. Moreover, zinc induction of exogenous wild-type IGFIIR expression reproducibly decreased growth rate and increased apoptosis. These data prove that wild-type IGFIIR functions as a growth suppressor gene in colorectal cancer cells and provide dynamic in vitro functional support for the hypothesis that IGFIIR is a human growth suppressor gene.

Original languageEnglish (US)
Pages (from-to)4063-4068
Number of pages6
JournalOncogene
Volume18
Issue number28
DOIs
StatePublished - Jul 15 1999

Keywords

  • Apoptosis
  • Colon cancer
  • Growth
  • Insulin-like growth factor II receptor
  • Microsatellite instability

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Souza, R. F., Wang, S., Thakar, M., Smolinski, K. N., Yin, J., Zou, T. T., Kong, D., Abraham, J. M., Toretsky, J. A., & Meltzer, S. J. (1999). Expression of the wild-type insulin-like growth factor II receptor gene suppresses growth and causes death in colorectal carcinoma cells. Oncogene, 18(28), 4063-4068. https://doi.org/10.1038/sj.onc.1202768