Glucocorticoid Regulation of Transcription of the c-mycCellular Protooncogene in P1798 Cells

Abstract

Glucocorticoids regulate proliferation of lymphosarcoma P1798 in culture. Treatment with dexamethasone caused a redistribution of cells with respect to the cell cycle. A decrease in cells in S and G2 + M phases was observed. This was accompanied by a corresponding increase in G1 cells. Growth arrest was preceded by a rapid and precipitous decrease in the expression of the cellular c-myc gene. Restriction analysis of the c-myc gene indicated that this locus was neither amplified nor grossly rearranged in P1798 cells. Glucocorticoids caused a decrease in the abundance of c-myc mRNA. After 24 h in 0.1 microM dexamethasone, c-myc mRNA levels declined to less than 5% of control. Fifty percent inhibition occurred within 90 min. The effects of dexamethasone were completely reversible. The amount of c-myc mRNA returned to control levels within 4 h after withdrawal of the hormone. Nuclear run-on transcription analysis indicated that glucocorticoids regulate transcription of the c-myc gene in P1798 cells. Transcription of exons I and II was inhibited to the same extent, suggesting that glucocorticoids inhibit initiation of transcription. Inhibition of transcription may account for decreased expression of c-myc which may, in turn, account for the antiproliferative effects of the hormone.

Glucocorticoids Inhibit Developmental Stage-specific Osteoblast Cell Cycle

“…Remarkably, however, this effect is mediated via diverse mechanisms. For example, inhibition of lymphoid cell proliferation, which partly accounts for the anti-inflammatory property of GC, is mediated by a decrease in the levels of G 1 cyclin and cyclin-dependent kinases (CDKs), in particular cyclin D3 and CDK4 (18 -20), as well as c-Myc (21,22). By contrast, in both hepatoma and lung alveolar cells, GC-induced cell cycle arrest has been attributed to induction of the CDK inhibitor (CDI) p21 (23)(24)(25).…”

Transcriptional down-regulation of c-myc in human prostate carcinoma cells by the synthetic androgen mibolerone

“…The transcription rate for the PSA (prostate-specific antigen [Schulz et al, 1988D gene was increased 3 h after addition of mibolerone and subsequently declined towards pretreatment levels after 4 days (Figure 4) LNCaP cells: inhibition of proliferation, abrogation of anchorage-independent growth, morphological change, and reduction of c-myc RNA levels (Wolf et al, 1991 (Rories et al, 1989), and in the murine lymphosarcoma cell line P1798 (Forsthoefel & Thompson, 1987). A direct transcriptional repression of the murine c-m)c gene by binding of the glucocorticoid receptor complex to a response element upstream of exon 1 has been discussed as a possible mechanism of c-myc shutoff (Forsthoefel & Thompson, 1987).…”

“…A direct transcriptional repression of the murine c-m)c gene by binding of the glucocorticoid receptor complex to a response element upstream of exon 1 has been discussed as a possible mechanism of c-myc shutoff (Forsthoefel & Thompson, 1987).…”

Mmip-2/Rnf-17 enhances c-Myc function and regulates some target genes in common with glucocorticoid hormones

“…GCs generally block proliferation, enhance dierentiation and promote apoptosis (Longenecker et al, 1984;Beato et al, 1995;MacDougald and Lane, 1995). In the case of lymphoid cells, where the eects of GCs on proliferation and apoptosis are particularly pronounced, a marked reduction in c-Myc levels is associated with GC-induced G 0 arrest which can be overcome by the enforced expression of c-Myc (Forsthoefel and Thompson, 1987;Thulasi et al, 1993;Rhee et al, 1995). On the other hand GCs, like c-Myc, can enhance proliferation and inhibit dierentiation in certain hematopoietic systems (Golde et al, 1976;Scher et al, 1978;von Lindern et al, 1999).…”