A comparative immunohistochemical study of spontaneous and chemically induced pheochromocytomas in B6C3F1 mice |
| |
Authors: | Hill Georgette D Pace Virgilio Persohn Elke Bresser Christina Haseman Joseph K Tischler Arthur S Nyska Abraham |
| |
Institution: | (1) Laboratory of Experimental Pathology, National Institute of Environmental Health Science (NIEHS), PO Box 12233, MD B3-06, 27709 Research Triangle Park, North Carolina, USA;(2) Biostatistics Branch, National Institute of Environmental Health Science (NIEHS), 27709 Research Triangle Park, North Carolina, USA;(3) Dompe SpA, R&D, Via Campo di Pile 1, 67100 L'Aquila, Italy;(4) Novartis Pharma AG, Auhafenstrasse, CH-4132 Muttenz, Switzerland;(5) Department of Pathology, New England Medical Center, 02111 Boston, MA |
| |
Abstract: | Spontaneously occurring and chemically induced pheochromocytomas are rare in mice. That the mouse pheochromocytoma is a more
appropriate animal model than that of the rat for study of human medullary adrenal tumors has been suggested. The expression
of phenylethanolamine-N-methyltransferase (PNMT), the enzyme responsible for production of epinephrine from norepinephrine,
is common to both mouse and human pheochromocytomas. This investigation assessed the expression of the immunohistochemical
markers PNMT, tyrosine hydroxylase (TH), and chromogranin A (CGA) in spontaneously occurring and chemically induced pheochromocytomas
in the B6C3F1 mouse. Spontaneous tumors were derived from control animals from 10 different studies and the pheochromocytomas
from treated groups from 4 different studies. All tumors were positive for maximal TH expression. A highly significant difference
in PNMT expression (p<0.01) occurred between spontaneously occurring pheochromocytomas classified as benign or “malignant” by the criteria of toxicologic
pathology. Chemically induced tumors showed intermediate PNMT staining. A marked reduction in CGA expression occurred in pheochromocytomas
induced by technical grade pentachlorophenol, compared to the other three chemicals and the spontaneously occurring tumors.
These findings suggest that immunohistochemistry is a reliable tool in investigating the functional capabilities of pheochromocytomas
in mice. PNMT expression is a tightly regulated component of the chromaffin cell phenotype and appears to be readily lost
in mouse pheochromocytomas, particularly those with aggressive characteristics. |
| |
Keywords: | Pheochromocytoma spontaneous chemically induced immunohistochmistry B6C3F1 mouse |
本文献已被 PubMed SpringerLink 等数据库收录! |
|