Growth Inhibition by Cholera Toxin of Human Lung Carcinoma Cell Lines: Correlation with GMi Ganglioside Expression

Gurmeet Kaur, Jean Viallet, Jorge Laborda, Owen Blair, Adi F. Gazdar, John D. Minna, Edward A. Sausville

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The effect of cholera toxin (CT) on the growth of 12 small cell lung carcinoma (SCLC) and 15 non-small cell lung carcinoma (NSCLC) cell lines is presented. CT inhibited the growth of nine SCLC cell lines (concentration for 50% inhibition of growth, 27-700 ng/ml), all of which had abundant expression of GMi ganglioside, the surface receptor for CT. CT-resistant SCLC all had greatly decreased GMi expression. In contrast, CT inhibited the growth of only four of 15 NSCLC cell lines. Seven of the 11 CT-resistant NSCLC had levels of GM, comparable to CT-sensitive NSCLC or SCLC. In a limited panel of cell lines, cyclic AMP (cAMP) agonists including forskolin, 8Br[cAMP], and dibutyryl(cAMP) did not consistently reproduce CT-mediated inhibition of cell growth, nor did these compounds overcome resistance of cells to the growth inhibitory effects of CT. Expression of the Ri and Rn regulatory subunits of cAMP-dependent protein kinase was similar in CT-resistant and CT-sensitive SCLC or NSCLC cell lines. In the presence of isobutylmethylxanthine, intracellular cAMP levels induced by CT in a CT-resistant, GMi(+) NSCLC cell line were comparable to those achieved in a CT-sensitive NSCLC cell line. We conclude that inhibition of lung carcinoma cell growth by CT in all cases requires expression of GMi, and in the case of SCLC cell lines the presence of GMi is sufficient. In NSCLC cell lines, expression of GMI is not sufficient for growth inhibition by CT. These findings imply refractoriness to growth inhibition by cAMP in GM)(+), CT-resistant NSCLC cell lines and the possibility of non-cAMP-related mechanisms for growth inhibition in CT-sensitive cell lines.

Original languageEnglish (US)
Pages (from-to)3340-3346
Number of pages7
JournalCancer research
Volume52
Issue number12
StatePublished - Jun 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kaur, G., Viallet, J., Laborda, J., Blair, O., Gazdar, A. F., Minna, J. D., & Sausville, E. A. (1992). Growth Inhibition by Cholera Toxin of Human Lung Carcinoma Cell Lines: Correlation with GMi Ganglioside Expression. Cancer research, 52(12), 3340-3346.