Introduction of nerve growth factor (NGF) receptors into a medulloblastoma cell line results in expression of high- And low-affinity NGF receptors but not NGF-mediated differentiation

Samuel J. Pleasure, Usha Rani Reddy, Gita Venkatakrishnan, Amit K. Roy, Jie Chen, Alonzo H. Ross, John Q. Trojanowski, David E Pleasure, Virginia M Y Lee

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Expression of the cloned human nerve growth factor receptor (NGFR) cDNA in cell lines can generate both high- and low-affinity binding sites. Since the inability to respond appropriately to differentiation factors such as NGF may contribute to determining the malignant phenotype of neurobiastomas, we sought to determine whether the same is true of medulloblastomas. To generate a human central nervous system neuronal cell line that would respond to NGF, we infected the medulloblastoma cell line D283 MED with a defective retrovirus carrying the cDNA coding for the human NGFR. The resultant cells (MED-NGFR) expressed abundant low- and high-affinity NGFRs, and NGF treatment induced a rapid transient increase of c-fos mRNA in the NGFR-expressing cells but not in the parent line or in cells infected with virus lacking the cDNA insert. However, the MED-NGFR cells did not internalize the NGFR at high efficiency, nor did they differentiate in response to NGF. Three important conclusions emerge from this study: (i) internalization of NGFRs is not necessary for some early rapid transcriptional effects of NGF; (ii) an unknown factor(s) that cooperates with the cloned NGFR in allowing high-affinity NGF binding is found in a primitive central nervous system cell line; and (iii) NGFRs introduced into and expressed by D283 MED (i.e., MED-NGFR) cells are partially functional but are unable to induce differentiation in these primitive neuron-like tumor cells, implying that high-efficiency receptor-mediated endocytosis of NGF and its receptor may be a necessary step in the cascade of events leading to NGF-mediated differentiation.

Original languageEnglish (US)
Pages (from-to)8496-8500
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number21
StatePublished - 1990
Externally publishedYes

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Nerve Growth Factor Receptors
Nerve Growth Factor Receptor
Medulloblastoma
Nerve Growth Factor
Cell Line
Complementary DNA
Central Nervous System
Retroviridae
Endocytosis
Binding Sites
Viruses
Phenotype
Neurons
Messenger RNA

Keywords

  • Endocytosis
  • Neuronal cell line
  • Primitive neuroectodermal tumors
  • Signal transduction

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Introduction of nerve growth factor (NGF) receptors into a medulloblastoma cell line results in expression of high- And low-affinity NGF receptors but not NGF-mediated differentiation. / Pleasure, Samuel J.; Reddy, Usha Rani; Venkatakrishnan, Gita; Roy, Amit K.; Chen, Jie; Ross, Alonzo H.; Trojanowski, John Q.; Pleasure, David E; Lee, Virginia M Y.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 21, 1990, p. 8496-8500.

Research output: Contribution to journalArticle

Pleasure, Samuel J. ; Reddy, Usha Rani ; Venkatakrishnan, Gita ; Roy, Amit K. ; Chen, Jie ; Ross, Alonzo H. ; Trojanowski, John Q. ; Pleasure, David E ; Lee, Virginia M Y. / Introduction of nerve growth factor (NGF) receptors into a medulloblastoma cell line results in expression of high- And low-affinity NGF receptors but not NGF-mediated differentiation. In: Proceedings of the National Academy of Sciences of the United States of America. 1990 ; Vol. 87, No. 21. pp. 8496-8500.
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abstract = "Expression of the cloned human nerve growth factor receptor (NGFR) cDNA in cell lines can generate both high- and low-affinity binding sites. Since the inability to respond appropriately to differentiation factors such as NGF may contribute to determining the malignant phenotype of neurobiastomas, we sought to determine whether the same is true of medulloblastomas. To generate a human central nervous system neuronal cell line that would respond to NGF, we infected the medulloblastoma cell line D283 MED with a defective retrovirus carrying the cDNA coding for the human NGFR. The resultant cells (MED-NGFR) expressed abundant low- and high-affinity NGFRs, and NGF treatment induced a rapid transient increase of c-fos mRNA in the NGFR-expressing cells but not in the parent line or in cells infected with virus lacking the cDNA insert. However, the MED-NGFR cells did not internalize the NGFR at high efficiency, nor did they differentiate in response to NGF. Three important conclusions emerge from this study: (i) internalization of NGFRs is not necessary for some early rapid transcriptional effects of NGF; (ii) an unknown factor(s) that cooperates with the cloned NGFR in allowing high-affinity NGF binding is found in a primitive central nervous system cell line; and (iii) NGFRs introduced into and expressed by D283 MED (i.e., MED-NGFR) cells are partially functional but are unable to induce differentiation in these primitive neuron-like tumor cells, implying that high-efficiency receptor-mediated endocytosis of NGF and its receptor may be a necessary step in the cascade of events leading to NGF-mediated differentiation.",
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T1 - Introduction of nerve growth factor (NGF) receptors into a medulloblastoma cell line results in expression of high- And low-affinity NGF receptors but not NGF-mediated differentiation

AU - Pleasure, Samuel J.

AU - Reddy, Usha Rani

AU - Venkatakrishnan, Gita

AU - Roy, Amit K.

AU - Chen, Jie

AU - Ross, Alonzo H.

AU - Trojanowski, John Q.

AU - Pleasure, David E

AU - Lee, Virginia M Y

PY - 1990

Y1 - 1990

N2 - Expression of the cloned human nerve growth factor receptor (NGFR) cDNA in cell lines can generate both high- and low-affinity binding sites. Since the inability to respond appropriately to differentiation factors such as NGF may contribute to determining the malignant phenotype of neurobiastomas, we sought to determine whether the same is true of medulloblastomas. To generate a human central nervous system neuronal cell line that would respond to NGF, we infected the medulloblastoma cell line D283 MED with a defective retrovirus carrying the cDNA coding for the human NGFR. The resultant cells (MED-NGFR) expressed abundant low- and high-affinity NGFRs, and NGF treatment induced a rapid transient increase of c-fos mRNA in the NGFR-expressing cells but not in the parent line or in cells infected with virus lacking the cDNA insert. However, the MED-NGFR cells did not internalize the NGFR at high efficiency, nor did they differentiate in response to NGF. Three important conclusions emerge from this study: (i) internalization of NGFRs is not necessary for some early rapid transcriptional effects of NGF; (ii) an unknown factor(s) that cooperates with the cloned NGFR in allowing high-affinity NGF binding is found in a primitive central nervous system cell line; and (iii) NGFRs introduced into and expressed by D283 MED (i.e., MED-NGFR) cells are partially functional but are unable to induce differentiation in these primitive neuron-like tumor cells, implying that high-efficiency receptor-mediated endocytosis of NGF and its receptor may be a necessary step in the cascade of events leading to NGF-mediated differentiation.

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