Pheochromocytoma cell lines from heterozygous neurofibromatosis knockout mice

• Published in: Cell and tissue research 2000-12, Vol.302 (3), p.309-320
• Main Authors: Powers, J F, Evinger, M J, Tsokas, P, Bedri, S, Alroy, J, Shahsavari, M, Tischler, A S
• Format: Article
• Language: English
• Subjects: 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; Receptor, trkA - metabolism; Reserpine - pharmacology; RNA, Messenger - biosynthesis; Transcription Factors; Transfection; Tumor Cells, Cultured
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s004410000290

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.