As the expression of histone H3 is restricted to the S phase of the cell cycle and therefore measures the growth fraction of a given population, we suggest that the increased expression of p53 observed in the large majority of colon tumors simply reflects the increased number of cycling cells frequently found in a neoplastic tissue.
Base excision repair of U:G mismatches at a mutational hotspot in the p53 gene is more efficient than base excision repair of T:G mismatches in extracts of human colon tumors.
Effect of sodium butyrate on the expression of retinoblastoma (RB1) and P53 gene and phosphorylation of retinoblastoma protein in human colon tumor cell line HT29.
C --> T transitions at CpG sites are the most prevalent mutations found in the p53 tumor suppressor gene in human colon tumors and in the germline (Li-Fraumeni syndrome).
To test that the targets of genetic instability could include critical transforming genes involved in colon tumor progression, we examined 23 colorectal carcinomas in patients with HNPCC in order to detect somatic mutations in K-ras and p53 genes.
Accumulating mutations of p53 in colon tumor and hairy cell leukemia do not arise from methylation/deamination processes, but rather from nucleotide deletions and insertions.
Although these results are consistent with the known role of wild-type p53 in down-regulating VEGF, no association was found between a mutation in p53 and VEGF or bFGF levels in all colonic neoplasms.
Identical LOH was detected in premalignant and malignant tissues in 4 of 17 patients, and was located at 5q21-q22 (D5S346 primer), 17p11.1-p12 (TCF2 primer), 17p13.1 (TP53 primer), 18q21.1 (detected in colon cancer tumor suppressor gene [DCC] primer), and 18q23-qter (D18S70 primer).
Interestingly, piroxicam was similarly effective in inhibiting colon tumor formation by DMH in mice with or without a mutation in the p53 tumor suppressor gene.
We show that 1) colon tumor cell lines expressing wild-type p53 are more sensitive to 5-aza-CdR mediated growth arrest and cytotoxicity; 2) the response to 5-aza-CdR treatment includes the induction and activation of wild-type but not mutant p53 protein; and 3) the induction of the downstream p53 target gene p21 is partially p53-dependent.
In this study we have investigated the effect of bile acids on the tumor suppressor p53 using the human colon tumor cell line HCT116, which retains the wild-type p53 gene and functional p53 signaling in response to DNA damage.
The data provide significant insight into mechanisms that establish colon tumor cell sensitivity to 5FU, clearly demonstrate the necessity of exercising caution in considering combining novel strategies that target elevated c-myc with standard 5FU-based therapy, and suggest alternative therapeutic strategies that target c-myc and/or p53 mutations in the treatment of colon cancer.
EndoV/Ligase mutation scanning combined with PCR/LDR/Universal array proved superior to automated DNA sequencing for detecting p53 mutations in colon tumors.