Activation and/or overexpression of the protein product of the ras gene family (p21ras) has been implicated in the development of various cancers, including bladder carcinoma.
Chromosomes isolated from a human bladder carcinoma cell line which contains the actively transforming oncogene HRAS1 on chromosome 11 can be used to transform mouse cells.
The effects of 7-hydroxycoumarin, genistein and quercetin on two ras-oncogene-driven tumour cells (rat breast adenocarcinoma and human bladder carcinoma) were investigated using cellular (proliferation and migration) and molecular targets (p21ras GTPase activity and intracellular amount of p21ras protein).
All together, co-existence of Aurora-A overexpression and Ha-ras mutation suggests a possible additively effect on the tumorigenesis of bladder cancer.
The induction of gene mutations and chromosome aberrations by plasmid pEJ6.6 carrying the activated c-Ha-ras-1 oncogene from human bladder carcinoma was studied in cultured Chinese hamster cells.
The c-Ha-ras-1 locus was studied by Southern blotting in white blood cells and tumor samples obtained from 126 patients with bladder cancer (74 Ta-T1 and 52 T2-T4).
The observation that these cell lines have p53 and Ha-ras mutations identical to those in bladder carcinoma cell line T24 prompted us to investigate their possible interrelations.
Analysis of HRAS gene TRR methylation showed that the methylation level of HRAS has clinical relevance (P = 0.0049, by unpaired Student's t test) with bladder cancer.
This starts with the new GhrasT-NIH/Swiss cell line that was produced from the NIH/3T3 cell line that had been transformed by transfection with HRAS oncogene DNA from the T24 human bladder carcinoma.
HRAS1 genotype may be related to the prognosis of bladder cancer, however, because incident cases, i.e., newly diagnosed cases had a higher frequency of rare alleles than did prevalent cases, i.e., cases already existing at the time of recruitment.
NIH 3T3 mouse fibroblasts form nonmetastasizing fibrosarcomas upon transformation by the Ha-ras oncogene isolated from the EJ human bladder carcinoma cell line and subcutaneous inoculation into immunocompetent NFS/NCr mice.
DNA sequence analysis of the activated oncogene from the T24 human bladder carcinoma line and two alleles of its normal cellular progenitor (c-Ha-ras-1) indicates that the genes encompass at least four exons, and that only a single point mutation residing within the first exon distinguishes the coding region of both alleles of the normal gene from their activated counterpart.
On the other hand, deletion of one Ha-ras allele was observed in 1 of 5 cases of bladder cancer and in 2 of 3 cases of renal pelvic cancer, suggesting that that deletion may be important in the development of urothelial cancer.