Gene Mutations in Animal Models: Do Tumor Suppressor Genes, brca1 and brca2, Play a Role in Ovarian Carcinogenesis?.
10.5625/lar.2010.26.4.323
- Author:
Bo Rim YI
1
;
Kyung A HWANG
;
Kyung Chul CHOI
Author Information
1. Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea. kchoi@cbu.ac.kr
- Publication Type:Review
- Keywords:
Ovarian surface epithelium;
tumor suppressor gene;
brca1/2;
animal models
- MeSH:
Animals;
Apoptosis;
Cause of Death;
Cell Cycle Checkpoints;
Cell Transformation, Neoplastic;
Cytokines;
DNA Repair;
Epithelium;
Female;
Genes, BRCA2;
Genes, Tumor Suppressor;
Genome;
Humans;
Intercellular Signaling Peptides and Proteins;
Mice;
Models, Animal;
NF-kappa B;
Ovarian Neoplasms;
Ovary;
Western World
- From:Laboratory Animal Research
2010;26(4):323-330
- CountryRepublic of Korea
- Language:English
-
Abstract:
Ovarian cancer is the most lethal cause of death from gynecological malignancies in the Western world. Over 90% of human ovarian cancers arise in the ovarian surface epithelium (OSE). The OSE surrounding the ovary is simple mesothelium and squamous to flat-cubobidal mesothelial cells. This cell type of ovary has both epithelial and mesenchymal potential. Also OSE cells are regulated by many factors such as cytokines, growth factors, and multiple hormones. Nevertheless OSE function is poorly understood. In particular, ovarian cancers are closely related with hereditary predisposition. Hereditary ovarian tumors are commonly associated with mutations in tumor suppressor genes such as brca1 and brca2 genes. These genes play a role in maintenance of genome integrity, DNA repair, cell cycle control and apoptosis. Mutations in brca1 and/or brca2 may lead to carcinogenesis through distinct molecular pathways like estrogen-mediated proliferation, the presence of a p53 mutation, and the modulation of the activity of NF-kB. Especially the dysfunction of brca1 triggers the inactivation of p53 and a higher proportion of a p53 mutation is commonly linked to brca-linked ovarian tumorigenesis. The dysfunction of brca1 and/or brca2 can arise from multiple mechanisms in the regulation of both JNK and ERK1/2 signaling. For more effective diagnosis and therapy of ovarian cancer, the role of brca1 and/or brca2 in ovarian cancer has to be distinctively elucidated by the animal models in which the gene functions are deleted in mouse OSE cells and by the mechanisms by which these genes affect ovarian carcinogenesis.
