Cholera toxin inhibits signal transduction by several mitogens and the in vitro growth of human small-cell lung cancer.
AUTOR(ES)
Viallet, J
RESUMO
Cholera toxin (CT) inhibited the in vitro growth of three of four human small-cell lung carcinoma (SCLC) cell lines with a 50% inhibitory concentration of 27-242 ng/ml. Loss of surface membrane ruffling and the capacity of [Tyr4]-bombesin, vasopressin, and fetal calf serum to stimulate increases in intracellular free calcium clearly preceded effects on cellular metabolic activity and cell growth. 125I-[Tyr4]-bombesin binding was unaffected by CT treatment but [Tyr4]-bombesin stimulated phospholipase C activity was decreased in membranes from CT-treated SCLC cells. CT stimulated a rapid but transient increase in intracellular cyclic AMP ([cAMP]i) in SCLC. The effects of CT on susceptible SCLC were not reproduced by elevations of [cAMP]i induced by forskolin or cyclic AMP analogues. GM1 ganglioside, the cellular binding site for CT, was highly expressed in the CT-sensitive but not the CT-resistant SCLC cell lines. In contrast, expression of guanine nucleotide binding protein substrates for ADP-ribosylation by CT was similar. These data demonstrate the existence of a CT-sensitive growth inhibitory pathway in SCLC-bearing GM1 ganglioside. Addition of CT results in decreased responsiveness to several mitogenic stimuli. These results suggest novel therapeutic approaches to human SCLC.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=329825Documentos Relacionados
- Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo
- Intrachromosomal rearrangements fusing L-myc and rlf in small-cell lung cancer.
- A unique cell-surface protein phenotype distinguishes human small-cell from non-small-cell lung cancer.
- Treatment of Small-Cell Lung Cancer
- Multiple mechanisms for transcriptional regulation of the myc gene family in small-cell lung cancer.