Cell Growth & Differentiation, Vol 1, Issue 9 421-428, Copyright © 1990 by American Association of Cancer Research

ARTICLES

Multiple defects of the nerve growth factor receptor in human neuroblastomas

CG Azar, NJ Scavarda, CP Reynolds and GM Brodeur
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110.

Neuroblastoma is a tumor of postganglionic sympathetic origin, and nerve growth factor (NGF) is normally required for the survival and differentiation of sympathetic neuroblasts. Since the biological activity of NGF is mediated by the NGF receptor (NGFR), we hypothesized that defects in the NGF/NGFR pathway may play a role in maintenance of the undifferentiated state of neuroblastomas. To test this hypothesis, we examined the structure of the NGFR at the DNA, RNA, and protein levels in a panel of 10 neuroblastoma cell lines. In addition, we examined the function of the NGFR in these lines by analysis of NGF binding kinetics, as well as by the ability of NGF to induce c-fos expression and neurite outgrowth. Southern blot analysis showed that all 10 cell lines possess apparently normal NGFR genes. Northern blot and ligand binding/immunoprecipitation assays revealed four receptor-positive cell lines (NGP, NLF, SK-N-SH, and LA-N-6), with NGFR mRNA and protein of expected sizes (3.8 kilobases and Mr approximately 75,000, respectively). NGF binding assays and Scatchard analyses were performed on the four NGFR-positive lines. The NGP line possesses only low-affinity receptor (Kd approximately 3.5 x 10(-9)), whereas the other three lines express both low- and high-affinity forms (Kd approximately 10(-9) and Kd approximately 10(-11), respectively). However, none of the 10 lines exhibited a response to NGF treatment as assayed by c-fos mRNA induction and neurite extension.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				K. Yamauchi, M. Tozuka, E. Hidaka, I. Ueno, K. Matsuda, and T. Katsuyama Internalization of {beta}-Amyloid Causes Downregulation of Apolipoprotein E mRNA Expression in Neuroblastoma Cells Ann. Clin. Lab. Sci., January 1, 2003; 33(1): 68 - 78. [Abstract] [Full Text] [PDF]

				K. Yamauchi, M. Tozuka, H. Hidaka, T. Nakabayashi, M. Sugano, and T. Katsuyama Isoform-specific Effect of Apolipoprotein E on Endocytosis of {beta}-Amyloid in Cultures of Neuroblastoma Cells Ann. Clin. Lab. Sci., January 1, 2002; 32(1): 65 - 74. [Abstract] [Full Text] [PDF]

				A. Edsjö, B. Hallberg, S. Fagerström, C. Larsson, H. Axelson, and S. Påhlman Differences in Early and Late Responses between Neurotrophin-stimulated trkA- and trkC-transfected SH-SY5Y Neuroblastoma Cells Cell Growth Differ., January 1, 2001; 12(1): 39 - 50. [Abstract] [Full Text]

				C. J. Kim, T. Matsuo, K.-H. Lee, and C. J. Thiele Up-Regulation of Insulin-Like Growth Factor-II Expression Is a Feature of TrkA but Not TrkB Activation in SH-SY5Y Neuroblastoma Cells Am. J. Pathol., November 1, 1999; 155(5): 1661 - 1670. [Abstract] [Full Text] [PDF]

				B. B. Chang, S. P. Persengiev, J. G. de Diego, M. P. Sacristan, D. M. Zanca, and D. L. Kilpatrick Proximal Promoter Sequences Mediate Cell-specific and Elevated Expression of the Favorable Prognosis Marker TrkA in Human Neuroblastoma Cells J. Biol. Chem., January 2, 1998; 273(1): 39 - 44. [Abstract] [Full Text] [PDF]

				A. Nakagawara, M. Arima-Nakagawara, N. J. Scavarda, C. G. Azar, A. B. Cantor, and G. M. Brodeur Association between High Levels of Expression of the TRK Gene and Favorable Outcome in Human Neuroblastoma N. Engl. J. Med., March 25, 1993; 328(12): 847 - 854. [Abstract] [Full Text]