title: Lack of Rev7 function results in development of tubulostromal adenomas in mouse ovary.
abstract: Rev7 is a subunit of Polζ, one of the translesion DNA synthesis (TLS) polymerases involved in DNA damage repair. We recently found that Rev7 is also essential for germ cell development in mouse. In the present study, we found the development of ovarian tumors in Rev7 mutant mouse, suggesting the involvement of TLS deficiency in the etiology of ovarian tumor. The Rev7 mutant mice showed complete lack of oocytes and follicles in the ovary. The lack of follicles causes a significant increase of gonadotropin level and an increase in the proliferation of ovarian cells. As a result, the weight of the ovaries of Rev7 mutant mice increased with age and they developed tubulostromal adenomas. However, the remarkable overgrowth of ovaries occurred after gonadotropin level decreases at older ages, suggesting gonadotropin-independent progression of the ovarian tumors. In addition, the Rev7 mutant fibroblasts and ovarian cells showed significant accumulation of DNA damage. These findings suggest that not only increased gonadotropin levels but also lack of DNA damage repair function could be responsible for the development of ovarian tumors in the Rev7 mutant mouse.
authors.affiliation: Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka, Okayama 700-8530, Japan; Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Abdolrahim
authors.initials: A
authors.lastname: Abbasi
authors.affiliation: Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka, Okayama 700-8530, Japan; Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khalaj
authors.affiliation: Advanced Science Research Center, Okayama University, Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Kouyou
authors.initials: K
authors.lastname: Akiyama
authors.affiliation: Faculty of Agriculture, Okayama University, Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mukai
authors.affiliation: Graduate School of Environmental and Life Science, Okayama University, Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Environmental and Life Science, Okayama University, Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Tomas J
authors.initials: TJ
authors.lastname: Acosta
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Virginia, Charlottesville, VA 22908-0422, USA.
authors.forename: Neveen
authors.initials: N
authors.lastname: Said
authors.affiliation: National Institute of Health Sciences, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Graduate School of Environmental and Life Science, Okayama University, Tsushima-naka, Okayama 700-8530, Japan. Electronic address: tkunieda@okayama-u.ac.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kunieda
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D063646:Carcinogenesis; D002478:Cells, Cultured; D004249:DNA Damage; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D064246:Mad2 Proteins / Q000235:genetics* / Q000378:metabolism; D008822:Mice, Transgenic; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology
chemical_list: D064246:Mad2 Proteins; C577699:Mad2l2 protein, mouse; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: Gonadotropin; Ovarian tumors; Rev7; Translesion DNA polymerase