c-Myc suppresses the tumorigenicity of lung cancer cells and down- regulates vascular endothelial growth factor expression

Linda F. Barr, Susan E. Campbell, Gregory B. Diette, Edward W. Gabrielson, Sunkyu Kim, Hyunsuk Shim, Chi V. Dang

Research output: Contribution to journalArticle

Abstract

The c-myc oncogene is frequently amplified in cells grown from lung tumors and has been linked to the malignancy of these cancers. In support of this, c-myc transfection enhances the in vitro proliferation and soft agar cloning of human small cell lung cancer (SCLC) cells. In this study, we surprisingly found that c-myc expression suppressed the formation of tumors by SCLC cells in athymic nude mice. c-myc expression down-regulated the protein and transcript for vascular endothelial growth factor (VEGF) in these SCLC cells, as well as VEGF transcript in rat fibroblasts manipulated for c- myc expression and in liver cells of c-myc-transgenic mice. Finally, bivariate and multivariate analyses demonstrated that the probability of tumor formation from lung cancer cell lines was negatively correlated with the relative expression c-Myc, positively correlated with the relative expression of VEGF, and that the latent time to tumor formation was increased by the expression of c-Myc and decreased by the expression of VEGF. We hypothesize that, for lung cancer cells, c-Myc suppresses the formation of tumors in vivo by down-regulating VEGF, and that the amplification of c-myc seen in cells grown from lung tumors with a poor prognosis is an artifact of selection for growth in vitro.

Original languageEnglish (US)
Pages (from-to)143-149
Number of pages7
JournalCancer Research
Volume60
Issue number1
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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