Regulation of c-myc and c-Ha-ras oncogene expression by cell shape

✍ Scribed by Robert E. Farrell Jr.; James J. Greene

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 740 KB
• Volume: 153
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041530223

✦ Synopsis

The influence of cell shape on the expression of proto-oncogenes was examined in normal and malignant human cells that varied in their sensitivities to contactinhibition of proliferation. Cells were constrained into varying degrees of roundness by plating onto culturc surfaces coated with different concentrations of poly(2-hydroxyethyl methacrylate) (poly [HEMA]) and assayed for proliferation capacity and levels of c-myc, c-ras, c-fos, and c-fes mRNAs. Proliferation of contact-inhibited normal CUA-1 fibroblasts and the variant HT-IFN' cells was highly coupled to cell shape. As these cells became more rounded, a critical degree of roundness was reached at which proliferation ceased. In contrast, proliferation of non-contact-inhibited malignant HT-1080 cells was independent of cell shape. Northern analysis revealed that expression of c-myc and C-ras was highly sensitive to cell shape in the normal CUA-1 cells but not in the malignant HT-1080 or variant HT-IFN' cells. Levels of c-myc and c -r a ~ mRNAs declined to nearly undetectable levels in CUA-1 cells at degrees of roundness that correlated with loss of proliferative ability. Expression of c-fos and c-fes oncogenes were independent of cell shape in all cells tested. Quantification of transcription rates by the nuclear run-off assay showed that shape modulation of c-myc and c-ras oncogene expression occurred at the transcriptional level. These data suggest that changes in cell shape can modulate expression of certain oncogenes and that these changes correlate with the cell's ability to proliferate. Moreover, inability to regulate c-myc and c-ras oncogene expression is associated with loss of shapedependent growth controls and contact inhibition but that loss of this regulation alone is not sufficient to release cells from contact-inhibited controls.