MMTV-neu mice deficient in STAT1 are susceptible to develop ovarian teratomas
Short Communication | Published: 23 April 2012
Lára Hannesdóttir1, Nina Daschil1, Sonja Philipp1, Piotr Tymoszuk1, Elisabeth Müller-Holzner2, Günter Klima3, Irmgard Verdorfer4 and Wolfgang Doppler*,1
1Division of Medical Biochemistry, Biocenter, 2Department of Obstetrics and Gynecology, 3Division of Histology and Embryology, Department of Anatomy, Histology, and Embryology and 4Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
Signal transducer and activator of transcription 1 (STAT1) serves in the protection of the organism against pathogens and other harmful insults. It is implicated in innate immune response, immunosurveillance, tumor-suppression, and the response to genotoxic as well as oxidative stress. We report here that 9 of 140 examined STAT1 deficient mouse mammary tumor virus-neu (MMTV-neu) mice developed differentiated ovarian teratomas, which histologically resemble benign dermatoid cysts. Conventional karyotyping revealed diploidy without structural rearrangements of the chromosomes. STAT1 proficient MMTV-neu mice with the same genetic background (FVB/N), and STAT1 deficient C57BL/6 mice failed to develop this type of tumor. This indicates that STAT1 deficiency promotes teratoma formation and this depends on MMTV-neu expression and/or the genetic background. Since ovarian teratomas are considered to develop as a consequence of alterations in the maturation of oocytes and follicular cells, we compared the ovaries from non-tumor bearing STAT1 deficient and proficient MMTV-neu mice. No detectable alterations in the number and proportion of the different follicular developmental stages were detected, implying the absence of non-redundant functions of STAT1 in normal folliculogenesis, as well as in follicular atresia. However, strong staining for STAT1 was detectable in granulosa and theca cells. These results point to a role for STAT1 in protecting from teratoma formation in a later step of tumorigenesis, e.g. by inducing apoptosis and eliminating premature or aberrantly formed follicles which have the potential to transform into teratomas.