Expression of the c-Ha-ras and neu oncogenes in DMBA-induced, anti-estrogen-treated rat mammary tumors.
Dimethylbenzanthracene (DMBA)-induced rat mammary tumors were analyzed for the structure and expression of the oncogenes c-Ha-ras and neu and the effects of anti-estrogen treatment. Tumor samples were divided into 3 groups, the first consisting of untreated tumors, the second of anti-estrogen (toremifene)-treated unresponsive (growing) tumors, and the third of toremifene-treated responsive (regressing) tumors. DNA and RNA derived from normal tissues of the same experimental animals were also analyzed. In Southern blot analysis of genomic DNAs, 2 tumors out of 23 contained a new Xbal site in the Ha-ras gene, indicating a point mutation in the second nucleotide of codon 61. Both of these tumors belonged to the group that had not received toremifene. No amplifications of the Ha-ras or the neu genes were observed. Although greatly variable, the levels of Ha-ras mRNA were highest in untreated tumors, lower in toremifene-treated, unresponsive tumors and even lower in toremifene-treated, regressing tumors, corresponding approximately to the levels detected in normal liver and uterus of untreated animals. Expression of the neu mRNA was variable and considerably lower than that of Ha-ras mRNA. It was similar in all 3 groups and somewhat elevated than in several non-malignant control tissues. Localization of c-Ha-ras expression by in situ hybridization revealed a relatively even distribution of the mRNA throughout the mammary tissue. The results suggest that mechanisms other than activation of the c-Ha-ras or neu genes are important for progression and regression of DMBA-induced rat mammary carcinomas.
Vuorio
T
T
Department of Medical Biochemistry, University of Turku, Finland.
Wärri
A
A
Sandberg
M
M
Alitalo
K
K
Vuorio
E
E
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004273:DNA, Neoplasm / Q000032:analysis; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D011905:Genes, ras; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics*; D009857:Oncogenes; D012334:RNA, Neoplasm / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000627:therapeutic use; D017312:Toremifene
D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; D012334:RNA, Neoplasm; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D017312:Toremifene; C025580:endodeoxyribonuclease XBAI; D015252:Deoxyribonucleases, Type II Site-Specific