The correlation between p53 mutations and the histological status of the samples suggest the involvement of this genetic event in the development of colon cancer in patients with ulcerative colitis.
Immunohistochemically, p53 protein expression was detected in 7/9 (78%) of radiation-induced cancers and in 23/42 (55%) of spontaneous colon cancers. chi 2 analysis found no significant differences between radiation-induced and spontaneous colon cancers in age distribution or p53-positive staining for frequency, histopathology, or Dukes' classification.
KM12L4 and SW620, human colon cancer cell lines with p53 mutations, were transduced with a replication-defective adenoviral vector containing the wild-type p53 gene (Ad5/CMV/p53).
A point mutation at codon 12 of the K-ras gene was found, while no alterations were noted in the p53 gene, whose mutations are frequent in colon cancers.
Unexpectedly, RER colon cancers bearing mutant p53 demonstrated the same stability of chromosome number, and the same stability of chromosome structure, as the RER colon cancers with wild-type p53.
In the present study, a large family with evidence of polyposis and colon cancer was screened for the mutations of the p53 gene and protein overexpression.
These results demonstrate that in a human colon epithelial cell background, wild-type p53 is functionally dominant over this mutant p53 and thus provides a mechanism for the observed inactivation of both copies of the p53 gene in most colon cancers.
We also find that induction of wild-type p53 potentiates the cytotoxicity of topotecan, a member of the camptothecin family of drugs that also has clinical activity against colon cancer.
Although the significance of this observation with respect to carcinogenesis remains to be established, the data suggest that ING1L might be involved in colon cancers through interference with signal(s) transmitted through p53 and p33(ING1).
We have studied the possible interactions between the mismatch repair system and p53 in a human colon cancer cell line, HCT-116 (known to have a homozygous mutation in mismatch repair gene hMLH1 on chromosome 3) and in a clone obtained after insertion of a single copy of chromosome 3 (HCT-116+ ch3).
We have examined the effects of commonly used chemotherapeutic agents on human colon cancer cell lines in which the p53 pathway has been specifically disrupted by targeted homologous recombination.
We applied the differential mRNA display method to isolate genes regulated by wild-type TP53 in cells of a colon-cancer line (SW480) in which we had established an inducible TP53 expression system under the control of the lactose operon.
In this study, to better understand the mechanism responsible for the p53-mediated apoptosis, the effect of wild-type p53 (wt-p53) gene transfer on nuclear expression of NF-kappaB was determined in human colon cancer cell lines.
Cytotoxicity assays showed that Adp14 had a statistically significantly (P =.002) greater effect on colon cancer (HCT116) cell lines containing two copies of the wild-type p53 gene than on p53-null cells, suggesting that functional p53 is a critical determinant of p14(ARF)-mediated cytotoxicity.
The biological characteristics of right-sided colon cancer were examined in 74 colon cancers with regard to clinicopathological parameters, proliferative activity and p53 expression.
GeneChip p53 assay demonstrated that a primary tumor sample from one colon cancer case had a heterozygous point mutation of CGT (Arg) to CAT (His) at codon 273 in exon 8.
Therefore, we suggest that Mn-SOD could be a target molecule to overcome the resistance to anti-cancer treatments in some colon cancer cells carrying wild-type p53.
We assessed the hypothesis that a compromised p53 function could account for the non response of colon cancer patients with low thymidylate synthase (TS) expression receiving a bolus 5-fluorouracil (5-FU) leucovorin (LV) combination.