c-FLIP: a key regulator of colorectal cancer cell death.

c-FLIP is an inhibitor of apoptosis mediated by the death receptors Fas, DR4, and DR5 and is expressed as long (c-FLIP(L)) and short (c-FLIP(S)) splice forms. We found that small interfering RNA (siRNA)-mediated silencing of c-FLIP induced spontaneous apoptosis in a panel of p53 wild-type, mutant, and null colorectal cancer cell lines and that this apoptosis was mediated by caspase-8 and Fas-associated death domain. Further analyses indicated the involvement of DR5 and/or Fas (but not DR4) in regulating apoptosis induced by c-FLIP siRNA.

Cellular FLICE-inhibitory protein regulates chemotherapy-induced apoptosis in breast cancer cells.

Combination treatment regimens that include topoisomerase-II-targeted drugs, such as doxorubicin, are widely used in the treatment of breast cancer. Previously, we showed that IFN-gamma and doxorubicin cotreatment synergistically induced apoptosis in MDA435 breast cancer cells in a signal transducer and activator of transcription 1-dependent manner. In this study, we found that this synergy was caspase-8 dependent.

Upregulation of MUC6 mucin gene expression by NFkappaB and Sp factors.

To clarify the mechanism underlying regulation of MUC6 expression, we isolated the 5' flanking region of the MUC6 gene (5'-MUC6). We determined the transcription start site of the MUC6 gene, and found a TATA box at -35 to -29bp, a putative NFkappaB consensus sequence at -173 to -164bp, and putative Sp family binding sites at -530 to -521 and -847 to -838bp. The luciferase activity of 5'-MUC6 gradually decreased with deletion of these sites.

Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients.

Epigenetic gene silencing through DNA methylation is one of the important steps in the mechanism underlying tumorigenesis, including in the stomach. Past lifestyle factors of cancer patients, such as intake of vegetables, are very important in affecting gastric carcinogenesis. However, the relationship between DNA methylation and past dietary habits in cancer patients remains largely unknown.

Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma.

SOX2, a SRY-related HMG box protein, is thought to be an important transcription factor during organogenesis, including the stomach although the expression and function are unclear. We investigated SOX2 protein expression to clarify its roles in differentiation and carcinogenesis of the stomach. Using polyclonal SOX2 antibodies, expression of SOX2 in gastric normal mucosae, intestinal metaplasia and carcinomas from 68 gastric carcinoma patients was studied by immuohistochemistry.

GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer.

The GATA family of transcription factors participates in gastrointestinal (GI) development. Increases in GATA-4 and -5 expression occur in differentiation and GATA-6 expression in proliferation in embryonic and adult settings. We now show that in colorectal cancer (CRC) and gastric cancer promoter hypermethylation and transcriptional silencing are frequent for GATA-4 and -5 but are never seen for GATA-6.