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 small cell lung cancer (SCLC) cells and contributes to the poor prognosis of this tumor. In this study, we confirm that transfected c-myc results 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 depleted, and flow cytometry suggests that this enhanced apoptosis is associated with a failure to halt cell cycling, consistent with the experience in other cell types. We previously found that protein kinase C-beta (PKC-beta) expression in NCI H209 (209) SCLC cells increases markedly with c-myc transfection (L. F. Barr et al., Cancer Res., 51: 5514-5519, 1991), and we hypothesized that PKC-beta may mediate some of the effects of c-myc in these cells. We test this hypothesis by transfection of rat PKC-beta 1 and bovine PKC-beta 2 isoforms into 209 cells before and after transfection with c-myc. PKC-beta 1 transfection has no effect on these cells. However, PKC-beta 2 expression has distinct phenotypic consequences. In the parental cells, PKC-beta 2 expression results in increased homotypic cell aggregation and a prolonged doubling time. Furthermore, PKC-beta 2 expression increases the fraction of these cells in G0-G1. In the cells which express a transfected c-myc gene, 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 G0-G1 fraction. We postulate that transfection of c-myc into SCLC cells may select for those expressing the PKC-beta 2 gene because this signal transduction event protects against myc-induced apoptosis.
Barr
L F
LF
Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland 21205, USA.
Campbell
S E
SE
Baylin
S B
SB
D000818:Animals; D017209:Apoptosis; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D002417:Cattle; D002449:Cell Aggregation; D002453:Cell Cycle; D008175:Lung Neoplasms / Q000378:metabolism*; D010641:Phenotype; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D014162:Transfection
D016271:Proto-Oncogene Proteins c-myc; D011493:Protein Kinase C; D064546:Protein Kinase C beta