Publication: Animal models of pheochromocytoma
Authors
Tischler, A.S. ; Powers, J.F. ; Alroy, J.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Pheochromocytomas are neuroendocrine
tumors of adrenal chromaffin cells. They are rare in all
species except rats but occur with increased frequency in
several human familial tumor syndromes. Concurrence
of pheochromocytoma with other tumors sometimes
parallels these human syndromes in rats, bovines, horses
and dogs but a shared genetic basis for human and
spontaneously occurring animal pheochromocytomas
has thus far not been established. Pheochromocytomas
are inducible in rats by a variety of non-genotoxic
substances that may act indirectly by stimulating
chromaffin cell proliferation. They are not known to be
similarly inducible in other species but arise with
increased frequency in transgenic and knockout mice
that to varying degrees recapitulate human tumor
syndromes. Preliminary evidence suggests that
homologous somatic genetic changes might contribute to
pheochromocytoma development in humans and some
mouse models. The nerve growth factor-responsive
PC12 cell line, established from a rat
pheochromocytoma, has for almost 30 years served as a
research tool for many aspects of neurobiology
involving normal and neoplastic conditions. Recently
developed pheochromocytoma cell lines from
neurofibromatosis knockout mice supplement the PC12
line and have generated additional applications. Advantages of the mouse lines include expression of
substantial levels of the epinephrine-synthesizing
enzyme, phenylethanolamine N-methyltransferase and
expression of high levels of the receptor tyrosine kinase,
Ret, which is characteristic of sporadic and familial
human pheochromocytomas but not of PC12 cells.
Disadvantages include an apparently less stable
phenotype. It is difficult to establish pheochromocytoma
cell lines from any species, although the tumor cells
persist in culture for many months. Understanding of
factors that permit pheochromocytoma cells to
proliferate might itself provide important insights for tumor biology.
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