Bcl-w expression in colorectal adenocarcinoma

Wilson, James W.; Nostro, M. Cristina; Balzi, Manuela; Faraoni, Paola; Cianchi, Fabio; Becciolini, Aldo; Potten, Christopher S

doi:10.1054/bjoc.1999.0897

Cited by 67 publications

(67 citation statements)

References 4 publications

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“…Some cancers, however, exhibit exclusive over-expression of one specific anti-apoptotic Bcl-2 protein. [11][12][13][14][15] For instance, in a study of head and neck carcinoma by Thompson et al, 52% of the patients had up-regulated Bcl-X L and 17% of the patients had upregulated Bcl-2. There was no overlap between these two groups.…”

Section: Introductionmentioning

confidence: 99%

Development of selective inhibitors for anti-apoptotic Bcl-2 proteins from BHI-1

Xing

Wang

Tang

et al. 2007

Bioorganic & Medicinal Chemistry

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A series of inhibitors for anti-apoptotic Bcl-2 proteins based on BHI-1 were synthesized and their binding interactions with Bcl-2, Bcl-X L , and Bcl-w were evaluated. It was found that modification of BHI-1 resulted in varied binding profiles among Bcl-2, Bcl-X L , and Bcl-w and a set of inhibitors with varied selectivity to Bcl-2, Bcl-X L , and Bcl-w protein have been identified. Molecular modeling of the interaction of the BHI-1 based analogs with the anti-apoptotic Bcl-2 proteins suggested that the binding site for the BHI-1 based inhibitor was the least conserved section among Bcl-2, Bcl-X L , and Bcl-w: targeting the non-conserved section may account for the observed selectivity of the BHI-1 based inhibitors among the anti-apoptotic Bcl-2 proteins. The validity of the model was supported by a strong correlation between the model-calculated binding energy and the experimental binding affinity. In summary, our studies suggest that most of the reported inhibitors for antiapoptotic Bcl-2 proteins are nonselective and BHI-1 is a promising template to distinguish among Bcl-2, Bcl-X L , and Bcl-w by targeting the nonconserved domain among the anti-apoptotic Bcl-2 proteins. Molecular-modeling aided rational development of BHI-1 based selective inhibitor for antiapoptotic Bcl-2 proteins is underway.

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Section: Introductionmentioning

confidence: 99%

Development of selective inhibitors for anti-apoptotic Bcl-2 proteins from BHI-1

Xing

Wang

Tang

et al. 2007

Bioorganic & Medicinal Chemistry

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“…Therefore, it has been suggested as an oncogene in several studies. Most importantly, expression of Id-1 has been found in many types of human cancers and its expression level has been indicated as a marker for malignant progression in a number of human cancers including the prostate (Desprez et al, 1998;Kleeff et al, 1998;Maruyama et al, 1999;Kebebew et al, 2000;Langlands et al, 2000;Polsky et al, 2001;Schindl et al, 2001;Takai et al, 2001;Wilson et al, 2001;Ouyang et al, 2002a). In a hormone-induced prostate cancer Noble rat model, we have found that Id-1 expression is increased with prostate cancer development from hyperplasia, dysplasia to malignancy (Ouyang et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Id-1 expression promotes cell survival through activation of NF-κB signalling pathway in prostate cancer cells

et al. 2003

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The growth-promoting effect of Id-1 (inhibitor of differentiation/DNA binding) has been demonstrated in a number of human cancers. However, the mechanisms responsible for its action are not clear. In this study, we report that in prostate cancer cells, Id-1 promotes cell survival through activation of nuclear factor-jB (NF-jB) signalling pathway. After stable expression of Id-1 protein in LNCaP cells, we found that the Id-1 transfectants showed increased resistance to apoptosis induced by TNFa through inactivation of Bax and caspase 3. In addition, in the LNCaP cells expressing ectopic Id-1 protein, we also observed increased NF-jB transactivation activity and nuclear translocation of the p65 and p50 proteins, which was accompanied by upregulation of their downstream effectors Bcl-xL and ICAM-1. These results indicate that the Id-1-induced antiapoptotic effect may be via NF-jB signalling transduction pathway in these cells. In addition, inactivation of Id-1 by its antisense oligonucleotide and retroviral construct in DU145 cells resulted in the decrease of nuclear level of p65 and p50 proteins, which was associated with increased sensitivity to TNFa-induced apoptosis. Our results strongly suggest that Id-1 may be one of the upstream regulators of NF-jB and activation of NF-jB signalling pathway may be essential for Id-1 induced cell proliferation through protection against apoptosis. Our findings also suggest a potential therapeutic strategy in which inactivation of Id-1 may lead to sensitization of prostate cancer cells to chemotherapeutic drug-induced apoptosis.

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“…Moderate expression of Id1, Id2 and Id3 in the normal colonic epithelium dramatically increases in colorectal human tumors and human colon carcinoma cell lines (Wilson et al, 2001). Ids have been implicated in several pathways central to colon carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells

et al. 2005

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1a,25-Dihydroxyvitamin D 3 (1a,25(OH) 2 D 3 ) has antitumor activity in addition to its classical action on calcium metabolism and bone tissue biology. It is thought to regulate the expression of multiple target genes and thus modulate processes critical for tumor growth and metastases. Here we show that 1a,25(OH) 2 D 3 differentially regulates the expression of Id1 and Id2 genes, members of a family of transcriptional regulators of cell proliferation and differentiation. 1a,25(OH) 2 D 3 induced epithelial differentiation in SW480-ADH human colon carcinoma cell line by promoting expression of the proteins implicated in adherent junction formation, including E-cadherin, and by inhibiting b-catenin transcriptional activity. 1a,25(OH) 2 D 3 activated the human Id1 gene promoter and rapidly induced Id1 RNA and protein. Ectopic overexpression of Id1 was not sufficient to induce E-cadherin, which was critical for the morphological changes induced by 1a,25(OH) 2 D 3 in SW480-ADH cells. Conversely, Id2 transcription rate, RNA and protein levels were decreased by 1a,25(OH) 2 D 3 . Id2 downregulation by 1a,25(OH) 2 D 3 mediated the antiproliferative effect of 1a,25(OH) 2 D 3 on SW480-ADH cells. In addition, we showed that 1a,25(OH) 2 D 3 changed the levels of the inducer of angiogenesis, vascular endothelial growth factor and the potent antiangiogenic factor thrombospondin-1, leading to a balanced change in the angiogenic potential of SW480-ADH human colon carcinoma cells.

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Bcl-w expression in colorectal adenocarcinoma

Cited by 67 publications

References 4 publications

Development of selective inhibitors for anti-apoptotic Bcl-2 proteins from BHI-1

Development of selective inhibitors for anti-apoptotic Bcl-2 proteins from BHI-1

Id-1 expression promotes cell survival through activation of NF-κB signalling pathway in prostate cancer cells

1α,25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells

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