Apoptosis Induced by c-Myc Overexpression Is Dependent on Growth Conditions

C‐myc gene expression alone is sufficient to confer resistance to antiestrogen in human breast cancer cells

“…37,38 It is also possible that MCF-7 were not sufficiently deprived of essential survival or growth factors because apoptosis associated with elevated c-myc expression in several cell types could take place only if the cells were deprived of survival factors. 3,28,29,39,40 The antiestrogen ICI 182,780 not only suppresses endogenous c-myc gene expression by blocking the action of estrogen at the level of the estrogen receptor, 12,15,16 but also affects the activities of bcl-2, 41 insulin-like growth factor binding protein 42 and receptor. 43 In addition, antiestrogens inhibit the expression of cyclin D1 44 and stimulate that of cdk inhibitors, p27 Kip1 and p21 Waf1/Cip1 .…”

Mechanisms of apoptosis by c-Myc

“…In a study of CHO cells overexpressing c-Myc, cell density was found to alter the susceptibility to death triggered by serum deprivation (Gibson et al, 1995). Cells cultured at higher densities were less susceptible, arguing that cell-cell interactions may limit death.…”

“…The following lines of evidence support this modi®ed dual signal model. First, it is possible in certain cases to arrest cells containing deregulated c-Myc without killing them (Gibson et al, 1995;Packham and Cleveland, 1996;Ryan and Birnie, 1997). For example, c-Myc-expressing 32D cells undergo growth arrest in the absence of cell death when treated with non-hydrolyzable analogs of cAMP (Packham and Cleveland, 1996).…”

Quiescence versus apoptosis: Myc abundance determines pathway of exit from the cell cycle

“…The expression of c-myc is activated when quiescent cells are stimulated to enter the cell cycle (Askew et al, 1991;Evan et al, 1992) and many neoplasias harbor translocated or ampli®ed c-myc genes, resulting in elevated Myc protein levels that are thought to contribute to cell cycle progression and an oncogenic state (Gibson et al, 1995;Lemaitre et al, 1996). Myc is a member of the helix ± loop ± helix/ leucine zipper transcription factor family and its function in growth regulation may be achieved by heterodimerization with Max protein and the activation of target genes via a CAC(G/A)TG nucleotide motif (Lemaitre et al, 1996).…”

“…Myc is a member of the helix ± loop ± helix/ leucine zipper transcription factor family and its function in growth regulation may be achieved by heterodimerization with Max protein and the activation of target genes via a CAC(G/A)TG nucleotide motif (Lemaitre et al, 1996). Curiously, the activation of c-myc genes can also enhance apoptosis in cells that are growth arrested (Askew et al, 1991;Evan et al, 1992;Gibson et al, 1995;Shi et al, 1992) and this enhancement can be attenuated by the cytokines, IGF-1 and PDGF (Harrington et al, 1994;O'Connor et al, 1997). How Myc can contribute to such disparate events as cell division and cell death remains unclear, nor is it known precisely how cellular responses to Myc might vary during progression from a normal to a tumorigenic state, where apoptosis associated with cmyc overexpression is not generally observed.…”