PROTEIN-KINASE C-BETA-2 INHIBITS CYCLING AND DECREASES C-MYC-INDUCED APOPTOSIS IN SMALL-CELL LUNG-CANCER CELLS

The overexpression of c-myc frequently accompanies the relapse of smal l cell lung cancer (SCLC) cells and contributes to the poor prognosis of this tumor, In this study, we confirm that transfected c-myc result s in decreased homotypic cell aggregation and increased proliferative capacity of SCLC cells when nutrient conditions are adequate, We also find that c-myc contributes to apoptosis when cells are nutrient deple ted, and flow cytometry suggests that this enhanced apoptosis is assoc iated with a failure to halt cell cycling, consistent with the experie nce in other cell types, We previously found that protein kinase C-bet a (PKC-beta) expression in NCI H209 (209) SCLC cells increases markedl y with c-myc transfection (L. F. Barr et al., Cancer Res., 51: 5514-55 19, 1991), and we hypothesized that PKC-beta may mediate some of the e ffects of c-myc in these cells, We test this hypothesis by transfectio n of rat PKC-beta 1 and bovine PKC-beta 2 isoforms into 209 cells befo re and after transfection with c-myc, PKC-beta 1 transfection has no e ffect on these cells. However, PKC-beta 2 expression has distinct phen otypic consequences. In the parental cells, PKC-beta 2 expression resu lts in increased homotypic cell aggregation and a prolonged doubling t ime, Furthermore, PKC-beta 2 expression increases the fraction of thes e cells in G(0)-G(1). In the cells which express a transfected c-myc g ene, PKC-beta 2 expression improves the survival of cells in low serum by decreasing myc-induced apoptosis, This effect was associated with, and may be mediated by, a selection for cells in the G(0)-G(1) fracti on, We postulate that transfection of c-myc into SCLC cells may select for those expressing the PKC-beta 2 gene because this signal transduc tion event protects against myc-induced apoptosis.