Increased inosine 5{prime}-monophosphate dehydrogenase gene expression in replicating cells: A response to growth factors, not to changes in cell cycle parameters
- Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology
The authors have analyzed levels of inosine 5{prime}-monophosphate dehydrogenase (IMPDH; E.C. 1.1.1.205) type II mRNA levels in a human melanoma cell line, SK-MEL-131, and a Chinese hamster ovary cell line synchronously progressing through the cell cycle following treatment with aphidicolin. Following release from the aphidicolin block at the G{sub 1}-S phase boundary, the type II IMPDH gene was found to be constitutively expressed at a similar level during all stages of the cell cycle. To analyze growth regulation, as opposed to cell cycle regulation, stable SK-MEL-131 transfectants that express a type II IMPDH-promoted heterologous construct were assayed following deprivation of serum growth factors and after restimulation with fresh serum. Serum deprivation resulted in down-regulation of both steady state type II IMPDH mRNA levels and promoter activity, while restimulation with serum resulted in up-regulation of these parameters. These findings support the conclusion that the increase in IMPDH type II gene expression in replicating cells is mainly due to growth factor regulation rather than changes in cell cycle parameters and that this regulation is mediated primarily by a transcriptional mechanism. The increased level of IMPDH expression and activity found in many tumors may therefore also be due to a transcriptionally mediated response to growth factors.
- Research Organization:
- Argonne National Lab., IL (United States)
- Sponsoring Organization:
- USDOE Office of Energy Research, Washington, DC (United States)
- DOE Contract Number:
- W-31109-ENG-38
- OSTI ID:
- 505322
- Report Number(s):
- ANL/CMB/PP--88357; ON: DE97007863
- Country of Publication:
- United States
- Language:
- English
Similar Records
p210 Bcr-Abl confers overexpression of inosine monophosphate dehydrogenase : an intrinsic pathway to drug resistance mediated by oncogene.
Chromosomal localization and structure of the human type II IMP dehydrogenase gene
Cloning, characterization, and regulation of the human type II IMP dehydrogenase gene
Journal Article
·
Fri Dec 31 23:00:00 EST 1993
· Leuk. Res.
·
OSTI ID:937699
Chromosomal localization and structure of the human type II IMP dehydrogenase gene
Technical Report
·
Sun May 01 00:00:00 EDT 1994
·
OSTI ID:10148872
Cloning, characterization, and regulation of the human type II IMP dehydrogenase gene
Technical Report
·
Tue Dec 31 23:00:00 EST 1996
·
OSTI ID:505306