Expression of Id helix-loop-helix proteins in colorectal adenocarcinoma correlates with p53 expression and mitotic index.
AuthorsWilson, James W
Deed, Richard W
Potten, Christopher S
Norton, John D
AffiliationCancer Research Campaign Epithelial Biology Group, Paterson Institute for Cancer Research, Christie Hospital, National Health Service Trust, Manchester M20 4BX, United Kingdom.
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AbstractId helix-loop-helix (HLH) proteins function as regulators of cell growth and differentiation and when overexpressed can induce malignant transformation. In a series of 34 cases of primary human colorectal adenocarcinoma, immunoreactivity for Id1, Id2, and Id3 was found to be significantly elevated in tumor compared with normal mucosa (P = 0.001 for Id1 and Id2; P = 0.002 for Id3). No elevation of Id expression was observed in 17 cases of adenoma. Expression of Id1 and to a lesser extent of Id2 was correlated with mitotic index (P = 0.005 for Id1; P = 0.042 for Id2) in human adenocarcinomas, and expression of all three Id proteins was correlated with p53 immunoreactivity (a marker of mutational 'inactivation' of p53 function; P = 0.002 for Id1; P = 0.006 for Id2; P = 0.016 for Id3). In normal intestinal mucosa of p53-null mice and in spontaneous tumors arising in Min+/- mice, expression of all three Id proteins was also found to be up-regulated. Antisense oligonucleotide blockade of Id protein expression inhibited the proliferation of human adenocarcinoma cells. Enforced, ectopic expression of the E47 basic HLH (bHLH) protein in human adenocarcinoma cell lines efficiently sequestered endogenous Id proteins as Id-bHLH heterodimers, as shown by coimmunoprecipitation and subcellular colocalization studies. This led to growth arrest of the cells. Enforced overexpression of a mutant E47 protein, deficient in transactivation and DNA binding function, also partially inhibited cell growth. Taken together, these data imply that deregulated expression of Id proteins in colorectal adenocarcinoma arises at least in part as a consequence of loss of p53 function and contributes to the uncontrolled proliferation of tumor cells in colorectal cancer.
CitationExpression of Id helix-loop-helix proteins in colorectal adenocarcinoma correlates with p53 expression and mitotic index. 2001, 61 (24):8803-10 Cancer Res.
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- Issue date: 2002 Jun
- Phosphorylation of helix-loop-helix proteins ID1, ID2 and ID3.
- Authors: Nagata Y, Shoji W, Obinata M, Todokoro K
- Issue date: 1995 Feb 27
- The helix-loop-helix protein Id2 is overexpressed in human pancreatic cancer.
- Authors: Kleeff J, Ishiwata T, Friess H, Büchler MW, Israel MA, Korc M
- Issue date: 1998 Sep 1
- A role for Id-1 in the aggressive phenotype and steroid hormone response of human breast cancer cells.
- Authors: Lin CQ, Singh J, Murata K, Itahana Y, Parrinello S, Liang SH, Gillett CE, Campisi J, Desprez PY
- Issue date: 2000 Mar 1
- Activation of helix-loop-helix proteins Id1, Id2 and Id3 during neural differentiation.
- Authors: Nagata Y, Todokoro K
- Issue date: 1994 Mar 30