Amplification and overexpression of c-myc proto-oncogene correlate with the loss of glucocorticoid dependence in rodent cells transformed by human papillomavirus type 16.
Transformation of baby mouse kidney epithelial cells by human papillomavirus (HPV) type 16 is dependent both upon the cooperating oncogene and on the hormonal conditions after transfection. With v-fos as the oncogene, the transformed cells require glucocorticoid hormone, such as dexamethasone, for proliferation. This requirement is lost on continued passage of cell lines, and the cells become dexamethasone independent. Steroid-independent cell lines are also produced by growth of the HPV16/v-fos cells in 17 beta-estradiol following transfection, but cell lines produced in this manner showed no subsequent requirement for estradiol or dexamethasone. Expression of the c-myc proto-oncogene was measured in dexamethasone-dependent and independent cell lines. Dexamethasone-dependent cell lines all exhibited low level c-myc expression, but this markedly increased in the cell lines that had become dexamethasone independent as a result of continued in vitro growth. The low level of c-myc expression in some early passage dexamethasone-dependent cell lines appears to be associated with rearrangement of the c-myc locus, whereas late passage dexamethasone-independent cell lines contain amplified c-myc sequences. Dexamethasone-independent cell lines derived by growth in 17 beta-estradiol showed higher levels of c-myc expression, together with higher c-myc copy number, than dexamethasone-dependent lines. Taken together, these studies indicate that the steady-state level of c-myc expression affects the continued requirement of HPV16-transformed cells for dexamethasone.
Crook
T
T
Department of Pathology, University of Cambridge, England.
Banks
L
L
Smith
K
K
Crawford
L
L
D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012313:RNA / Q000032:analysis
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D004958:Estradiol; D012313:RNA; D003907:Dexamethasone