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American Journal of Pathology, Vol 145, 1323-1336, Copyright © 1994 by American Society for Investigative Pathology

REGULAR ARTICLES

Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2

S Krajewski, M Krajewska, A Shabaik, T Miyashita, HG Wang and JC Reed
Oncogene and Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, California 92037.

The protein encoded by the bcl-2 gene is a regulator of programmed cell death and apoptosis. The cell survival-promoting activity of this protein is opposed by Bax, a homologous protein that forms heterodimers with Bcl-2 and accelerates rates of cell death. In this report, the in vivo patterns of bax gene expression were immunohistochemically assessed in the mouse, with a polyclonal antibody raised against a synthetic peptide corresponding to a unique region in the murine Bax protein. Direct comparisons were made with Bcl-2 by using anti-peptide antisera specific for the mouse Bcl-2 protein. The expression of bax was more widespread than bcl-2. For example, Bax immunoreactivity was present in the hepatocytes of the liver, the exocrine pancreas, and the renal tubule epithelial cells whereas Bcl-2 was absent from these tissues. Both the Bax and Bcl-2 proteins were present in several epithelia examined, including the small intestines, colon, breast, prostate, respiratory tract, and skin. The most intense Bax immunostaining was seen in cells located in the base of the crypts of the small intestinal mucosa, consistent with reports of high rates of spontaneous and inducible apoptosis in this region. Bcl-2 immunostaining was completely absent from these cells but was present in the absorptive epithelial cells of the small intestine. In contrast, Bax immunostaining in the colon tended to be stronger in the surface epithelial cells that had advanced up the crypts towards the lumen and that are destined for programmed cell death, whereas Bcl-2 immunoreactivity generally was stronger in the base of the colonic crypts. Similarly, bax expression in the gastric pits of the stomach occurred in a gradient such that higher levels of Bax immunostaining were found in the upper layers of gastric glands than in the lower regions. In addition, strong Bax immunostaining was detected in the androgen-dependent secretory epithelial cells of the prostate, whereas Bcl-2 was limited to the androgen-independent basal cells. Like Bcl-2, Bax was found in the thymic medulla but not the cortex, despite the propensity for immature cortical thymocytes to undergo apoptosis. Unlike Bcl-2, however, Bax immunostaining tended to be more intense in the germinal center lymphocytes of lymph nodes than in the interfollicular lymphocytes, consistent with the high rate of apoptotic cell death in the former.(ABSTRACT TRUNCATED AT 400 WORDS)


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A. Metcalfe, A Gilmore, T Klinowska, J Oliver, A. Valentijn, R Brown, A Ross, G MacGregor, J. Hickman, and C. Streuli
Developmental regulation of Bcl-2 family protein expression in the involuting mammary gland
J. Cell Sci., January 6, 1999; 112(11): 1771 - 1783.
[Abstract] [PDF]

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 CarcinogenesisHome page
S. Sanders and S. S. Thorgeirsson
Phenobarbital promotes liver growth in c-myc/TGF-{alpha} transgenic mice by inducing hypertrophy and inhibiting apoptosis
Carcinogenesis, January 1, 1999; 20(1): 41 - 49.
[Abstract] [Full Text] [PDF]

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 J. Virol.Home page
A. Lieber, C.-Y. He, L. Meuse, C. Himeda, C. Wilson, and M. A. Kay
Inhibition of NF-kappa B Activation in Combination with Bcl-2