Pheochromocytoma cell lines from heterozygous neurofibromatosis knockout mice

Cell Tissue Res. 2000 Dec;302(3):309-20. doi: 10.1007/s004410000290.

Abstract

Transplantable tumors and cell lines have been developed from pheochromocytomas arising in mice with a heterozygous knockout mutation of the neurofibromatosis gene, Nf1. Nf1 encodes a ras-GTPase-activating protein, neurofibromin, and mouse pheochromocytoma (MPC) cells in primary cultures typically show extensive spontaneous neuronal differentiation that may result from the loss of the remaining wild-type allele and defective regulation of ras signaling. However, all MPC cell lines express neurofibromin, suggesting that preservation of the wild-type allele may be required to permit the propagation of MPC cells in vitro. MPC lines differ from PC12 cells in that they express both endogenous phenylethanolamine N-methyltransferase (PNMT) and full-length PNMT reporter constructs. PNMT expression is increased by dexamethasone and by cell-cell contact in suspension cultures. Mouse pheochromocytomas are a new tool for studying genes and signaling pathways that regulate cell growth and differentiation in adrenal medullary neoplasms and are a unique model for studying the regulation of PNMT expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Gland Neoplasms / genetics*
  • Adrenal Gland Neoplasms / metabolism
  • Adrenal Gland Neoplasms / pathology
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression
  • Genes, Neurofibromatosis 1*
  • Genes, Reporter
  • Heterozygote
  • Male
  • Mice
  • Mice, Knockout
  • Neoplasm Transplantation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurofibromin 1
  • Nuclear Proteins / metabolism
  • Phenylethanolamine N-Methyltransferase / genetics
  • Phenylethanolamine N-Methyltransferase / metabolism
  • Pheochromocytoma / genetics*
  • Pheochromocytoma / metabolism
  • Pheochromocytoma / pathology
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Receptor, trkA / metabolism
  • Reserpine / pharmacology
  • Transcription Factors*
  • Transfection
  • Tumor Cells, Cultured*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Myc associated factor X
  • Nerve Tissue Proteins
  • Neurofibromin 1
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Max protein, mouse
  • Reserpine
  • Phenylethanolamine N-Methyltransferase
  • Receptor, trkA