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American Journal of Pathology, Vol 152, 1407-1413, Copyright © 1998 by American Society for Investigative Pathology

REGULAR ARTICLES

Bcl-2 and c-Myc, but not bax and p53, are expressed during human medullary thyroid tumorigenesis

DG Wang, WH Liu, CF Johnston, JM Sloan and KD Buchanan
Department of Medicine, School of Clinical Medicine, Queen's University of Belfast, United Kingdom.

Medullary thyroid carcinoma (MTC) is a tumor of parafollicular cells of the thyroid gland. It has served as a useful experimental model for the study of tumor proliferation and differentiation. Although recent studies have identified the gene involved in familial forms of MTC, little is known about the molecular pathogenesis of the sporadic variants of this tumor. It has become increasingly clear that deregulation of programmed cell death is a critical component in multistep tumorigenesis. The present investigation was undertaken to determine whether similar molecular events occur in human MTC. Eighteen MTCs from 18 patients (including 12 sporadic and six familial cases and one metastatic lymph gland) and a MTC cell line (TT cells) were used in this study for detecting the expression of apoptosis-regulatory genes bcl-2, bax, c-myc, and p53. Immunohistochemical results showed that all MTC tumor samples displayed Bcl-2 and c-Myc immunoreactivity, whereas only 4 and 2 tumors showed a minority of cells positive for Bax and p53, respectively. Western and Northern blotting showed high levels of 26-kd Bcl-2 protein and bcl-2 transcript. The co-expression of Bcl-2 and c-Myc was also detected in the TT cells by indirect fluorescence immunohistochemistry and Western blotting. Moreover, Bcl-2 immunoreactivity was also found in C-cell hyperplasia from familial patients indicating that expression of this oncogene may represent an early event in the pathogenesis of MTC. The present study suggests that deregulation of programmed cell death may be a critical component in multistep tumorigenesis of MTC and that the frequent expression of the Bcl-2 oncoprotein in these tumors may contribute to their pathogenesis. The genetic complementation of simultaneously deregulated bcl-2 and c- myc may be implicated in the multistep tumorigenesis of human MTC.

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