We have investigated the nature of the MspI site polymorphism at the c-Ha-ras VNTR observed in variety of tumors including breast cancer.We find that the MspI site 5' to the VNTR is present in a Non-B DNA structure with single-strand character that renders it accessible to bisulfite modification under native conditions, while the MspI site 3' to the VNTR appears to reside in a normal B-form structure that is inaccessible to bisulfite.
We analyzed 66 independent cases from sib pairs affected with breast cancer that had previously been collected during an investigation of pathogenetic-allele-sharing at the HRAS1 mini-satellite locus.
This study for the first time assayed the prognostic value and changes in the expression of SIRT3, LSP1, HRAS, SCUBE2 and AP2A2 genes in women with breast cancer in the Iranian population and findings confirmed potential biomarker and prognostic capability of these genes.
There was no support for an association between rare HRAS1 alleles and the risk of early-onset breast cancer, despite 80% power to detect effects of the magnitude of those associations (1.7-fold) previously suggested.
There may be more common mutations in other genes (such as ATM, HRAS1) that confer a moderate risk of breast cancer, and may account for 5 to 15 per cent of cases.
The study was done on a total of 51 lung, colon and breast carcinoma tumors using a panel of oligonucleotides coding for the wild type and all possible mutations in codons 12 and 61 of c-K-ras gene.
The results obtained with atypical hyperplasia, a doubtful proliferating lesion, suggests that p21 c-Ha-ras protein expression is not restricted to breast carcinomas.
The frequency of rare c-Ha-ras-1 alleles and hence genotypes composed of two rare alleles was increased in the breast cancer population (P less than .001).
The findings on Ha-ras and other informative loci are consistent with the possibility that a tumour suppressor gene involved in the early stages of breast cancer is located on the short arm of chromosome 11.
Since both estradiol treatment and ras-oncogene overexpression enhance tumorigenicity of hormone-dependent breast-cancer cells, we studied the effects of estrogen and of the activated v-Ha-ras oncogene on NK susceptibility of MCF-7 human breast-cancer cells.
Several epidemiologic studies suggest that individuals carrying rare alleles at a minisatellite flanking the HRAS locus are at increased risk of cancer, including breast cancer.
Our data demonstrate a direct (i) interaction of c-Ha-ras sequence with estrogen receptor and (ii) stimulatory effect of estrogen on c-Ha-ras gene transcription and suggest that alteration in transcriptional regulation of c-Ha-ras gene by estrogen may play an important role in progression of breast cancer.
Lod scores for close linkage of each candidate sequence to breast cancer were -19.6 for HRAS, -12.3 for KRAS2, -1.0 for NRAS, -6.0 for MYC, -6.1 for MYB, -8.2 for ERBA2, -7.9 for INT2, and -5.1 for RAF1.