This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaur, G. Articles by Sausville, E. A. Search for Related Content PubMed PubMed Citation Articles by Kaur, G. Articles by Sausville, E. A.

Growth Inhibition by Cholera Toxin of Human Lung Carcinoma Cell Lines: Correlation with G_M1 Ganglioside Expression¹

Laboratory of Biological Chemistry [G. K., E. A. S.], National Cancer Institute-Navy Medical Oncology Branch [J. V., A. F. G., J. D. M], National Cancer Institute, Bethesda, Maryland 20892, and Vincent T. Lombardi Cancer Research Center [J. L., O. B.], Georgetown University Medical Center, Washington, D.C. 20007

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 G_M1 ganglioside, the surface receptor for CT. CT-resistant SCLC all had greatly decreased G_M1 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 G_M1 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 R₁ and R_I1 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, G_M1(+) 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 G_M1, and in the case of SCLC cell lines the presence of G_M1 is sufficient. In NSCLC cell lines, expression of G_M1 is not sufficient for growth inhibition by CT. These findings imply refractoriness to growth inhibition by cAMP in G_M1(+), CT-resistant NSCLC cell lines and the possibility of non-cAMP-related mechanisms for growth inhibition in CT-sensitive cell lines.

¹ J. V. is a Scholar of the Medical Research Council of Canada and a recipient of a 1991 American Society of Clinical Oncology Young Investigator Award.

² Present address: Department of Oncology, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.

³ To whom requests for reprints should be addressed, at Laboratory of Biological Chemistry, NCI, Bldg. 37, Rm. 5D02, NIH, 9000 Rockville Pike, Bethesda, MD 20892.

Received 8/26/91. Accepted 4/ 3/92.

This article has been cited by other articles:

				Y. Koh, T. Tsunoda, M. Iwahashi, H. Yamaue, K. Ishimoto, H. Tanimura, H. Fukumoto, T. Nakamura, Y. Tatsumi, M. Shimizu, et al. Decreased Expression of {alpha}2,8 Sialyltransferase and Increased Expression of {beta}1,4 N-Acetylgalactosaminyltransferase in Gastrointestinal Cancers Experimental Biology and Medicine, March 1, 2002; 227(3): 196 - 200. [Abstract] [Full Text] [PDF]

				K. Nakamura, M. Hanibuchi, S. Yano, Y. Tanaka, I. Fujino, M. Inoue, T. Takezawa, K. Shitara, S. Sone, and N. Hanai Apoptosis Induction of Human Lung Cancer Cell Line in Multicellular Heterospheroids with Humanized Antiganglioside GM2 Monoclonal Antibody Cancer Res., October 1, 1999; 59(20): 5323 - 5330. [Abstract] [Full Text] [PDF]

				S. Cook and F McCormick Inhibition by cAMP of Ras-dependent activation of Raf Science, November 12, 1993; 262(5136): 1069 - 1072. [Abstract] [PDF]