Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia.
AffiliationCRC Department of Epithelial Biology, Paterson Institute, Manchester, UK.
MetadataShow full item record
AbstractThe cell-positional incidence of both spontaneous and damage-induced apoptosis of epithelial cells was assessed in longitudinal sections of the crypts of small intestine and colon of BDF1 mice. This was compared, using immunohistochemistry, with the pattern of expression of bcl-2, a suppressor of apoptosis. In the small intestine, apoptosis was maximal around cell position 4 from the base of the crypt; this closely corresponds to the position considered to contain the stem cells. In the colon, however, apoptosis was not confined to the area considered to harbour the stem cells (position 1 and 2). Instead, apoptosis was attenuated and distributed along the length of the crypt. Some cells at the base of murine colonic crypts expressed bcl-2 protein, whereas bcl-2 was absent in the crypts of the small intestine. Most pertinently, bcl-2 was absent from small intestinal crypt cells at positions 4-5 (the stem cell region). The importance of the expression of bcl-2 to the attenuation of apoptosis in stem cells was confirmed by analysis of the levels of both spontaneous and induced apoptosis in homozygously bcl-2 null C57BL/6 mice: in colonic crypts the level of spontaneous apoptosis rose significantly, and selectively at the base of the crypt, in comparison with crypts from wild-type animals. In contrast, there was no rise in spontaneous apoptosis in the small intestinal crypts from the bcl-2 null animals. Analysis of sections of human colon and small intestine also showed that expression of bcl-2 was confined to the base of the colonic crypt. The attenuation of apoptosis by bcl-2 in the region of the stem cells of the colonic crypts may dispose these to neoplastic transformation. Indeed, analysis of human carcinomas revealed expression of bcl-2, which in some samples was reciprocal with the expression of p53.
CitationDifferential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. 1995, 108 ( Pt 6):2261-71 J. Cell. Sci.
JournalJournal of Cell Science
- Damage-induced apoptosis in intestinal epithelia from bcl-2-null and bax-null mice: investigations of the mechanistic determinants of epithelial apoptosis in vivo.
- Authors: Pritchard DM, Potten CS, Korsmeyer SJ, Roberts S, Hickman JA
- Issue date: 1999 Dec 2
- Suppression of apoptosis, crypt hyperplasia, and altered differentiation in the colonic epithelia of bak-null mice.
- Authors: Duckworth CA, Pritchard DM
- Issue date: 2009 Mar
- Bcl-w is an important determinant of damage-induced apoptosis in epithelia of small and large intestine.
- Authors: Pritchard DM, Print C, O'Reilly L, Adams JM, Potten CS, Hickman JA
- Issue date: 2000 Aug 10
- Expression of Bcl-2 protein in hyperplastic polyps, adenomas, and carcinomas of the colon.
- Authors: Flohil CC, Janssen PA, Bosman FT
- Issue date: 1996 Apr
- Radiation-induced p53 and p21WAF-1/CIP1 expression in the murine intestinal epithelium: apoptosis and cell cycle arrest.
- Authors: Wilson JW, Pritchard DM, Hickman JA, Potten CS
- Issue date: 1998 Sep