Pheochromocytoma cell lines from heterozygous neurofibromatosis knockout mice.
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.
Powers
J F
JF
Department of Pathology, Box 802, New England Medical Center and Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA. jpowersl@lifespan.org
Evinger
M J
MJ
Tsokas
P
P
Bedri
S
S
Alroy
J
J
Shahsavari
M
M
Tischler
A S
AS
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D016514:Genes, Neurofibromatosis 1; D017930:Genes, Reporter; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D025542:Neurofibromin 1; D009687:Nuclear Proteins / Q000378:metabolism; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020917:Receptor, trkA / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C068422:Max protein, mouse; D012110:Reserpine; D010625:Phenylethanolamine N-Methyltransferase; D020917:Receptor, trkA