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Expression of the c‐Ha‐ ras and neu oncogenes in DMBA‐induced, anti‐estrogen‐treated rat mammary tumors
Author(s) -
Vuorio Tuula,
Wärri Anni,
Sandberg Minna,
Alitalo Kari,
Vuorio Eero
Publication year - 1988
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910420524
Subject(s) - dmba , toremifene , biology , messenger rna , estrogen , mammary gland , gene expression , in situ hybridization , microbiology and biotechnology , carcinogenesis , cancer , gene , medicine , endocrinology , cancer research , tamoxifen , breast cancer , genetics
Abstract 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 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.