Expression of Oncogenes Depends on Biotin in Human Small Cell Lung Cancer Cells NCl-H69

Sarah B. Scheerger, Janos Zempleni

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Oncogenes play important roles in cell proliferation and biotin status correlates with gene expression and proliferation rates in human cells. In this study we determined whether biotin supply affects biotin homeostasis, expression of oncogenes, and proliferation rates in NCI-H69 small cell lung cancer cells. NCI-H69 cells were cultured in media containing deficient (0.025 nmol/L), physiologic (0.25 nmol/L), or pharmacologic (10 nmol/L) concentrations of biotin for 3 weeks. Biotin concentrations in culture media correlated negatively with biotin transport rates, suggesting that cells responded to marginal biotin supply with increased expression of biotin transporters. Increased biotin uptake was not sufficient to prevent depletion of intracellular biotin in cells cultured in biotin-deficient medium, as judged by decreased activity of biotin-dependent propionyl-CoA carboxylase and decreased biotinylation of histones. The expression of oncogenes N-myc, c-myb, N-ras, and raf correlated with biotin supply in media: oncogene expression increased by up to 20% in cells cultured in pharmacologic medium compared to physiologic controls; oncogene expression decreased by up to 47% in cells cultured in deficient medium. This observation is consistent with a role for biotin in oncogene-dependent metabolic pathways. Cellular uptake of thymidine (marker for proliferation) was not affected by biotin supply, suggesting that effects of biotin-dependent expression of oncogenes on the growth of tumor cells are quantitatively minor. The clinical significance of effects of biotin supply on expression of oncogenes remains to be elaborated.

Original languageEnglish (US)
Pages (from-to)461-467
Number of pages7
JournalInternational Journal for Vitamin and Nutrition Research
Volume73
Issue number6
DOIs
StatePublished - Dec 2003

Keywords

  • Biotin
  • Human
  • Oncogenes
  • Proliferation
  • Small cell lung cancer cells

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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