Publication Year

2005

Keywords

Oncogenes, mice, non-synergistic, tumorigenesis, doxorubicin

Disciplines

Cancer Biology | Cell and Developmental Biology | Chemistry | Medicine and Health Sciences

Abstract

Doxorubicin, an anthracycline antibiotic, is one of the most widely used and effective antineoplastic agents used for the treatment of solid tumors, lymphomas, and acute lymphoblastic and myelocytic leukemias. Reduction of the C-13 carbonyl results in the formation of its cardiotoxic alcohol metabolite, doxorubicinol. Cbr1, a monomeric carbonyl reductase, is of special interest because its conversion of doxorubicin was found to occur most greatly in the heart. It was hypothesized that mouse models heterozygous for a Cbr1 null allele, which show a reduction in Cbr1 protein, would suffer less cardiotoxic side effects while showing a concomitant increase in the efficacy of doxorubicin treatment. Transgenic mouse models were used that coexpressed the MMTV.HER2/neu and MMTV.c-myc oncogenes. Tumor development for the coexpression of these oncogenes had not been characterized, but synergistic tumor development was hypothesized to occur. However, at the time the study concluded, synergenetic tumorgenesis did not occur. Overexpression of the HER2/neu oncogene has been shown to produce tumors with a T50 of 89 days while overexpression of the c-myc oncogene has been shown to produce tumors with a T50 of 325 days. After 173 days, no tumors developed, which was verified by histopathological analysis of mammary gland whole mounts. This left the hypothesis of doxorubicin efficacy unable to be tested. The delay in tumorgenesis is hypothesized to be due to interference in the pathways of HER2/neu and c-myc. Continued research on these oncogenes may lead to breakthroughs in effective ways to pharmaceutically treat HER2/neu-induced and c-myc-induced tumors.

Department 1 Awarding Honors Status

Biology

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