Expression profiling of homocysteine junction enzymes in the NCI60 panel of human cancer cell lines

Wen Zhang, Aaron Braun, Zachary Bauman, Horatiu Olteanu, Peter Madzelan, Ruma Banerjee

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Methionine metabolism provides two key cellular reagents: S-adenosylmethionine and glutathione, derived from the common intermediate, homocysteine. A majority of cancer cells exhibit a methionine-dependent phenotype whereby they are unable to grow in medium in which methionine is replaced by its precursor, homocysteine. Additionally, CpG island hypermethylation of tumor suppressor gene promoters is observed in a background of global hypomethylation in cancerous cells. In this study, we have profiled the expression levels of the homocysteine junction enzymes, methionine synthase (MS), MS reductase (MSR), and cystathionine β-synthase (CBS) in the NCI60 panel of cancer cell lines. The doubling time of non-small lung cell cancer lines, which exhibit the lowest levels of MS within the panel, was significantly correlated with expression of MS. The ratio of MS to MSR varied over a 5-fold range in the different cell types, which may modulate methionine synthesis. Interestingly, markedly reduced CBS expression was seen in the methionine-dependent prostate cancer cell line, PC-3, but not in the methionine-independent cell line, DU-145. However, neither provision of the transsulfuration pathway product, cysteine, nor overexpression of CBS rescued the growth impairment, indicating that reduced CBS was not responsible for the methionine-dependent phenotype in this cell line.

Original languageEnglish (US)
Pages (from-to)1554-1560
Number of pages7
JournalCancer research
Volume65
Issue number4
DOIs
StatePublished - Feb 15 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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