title: MMTV-neu mice deficient in STAT1 are susceptible to develop ovarian teratomas.
abstract: 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.
authors.affiliation: Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Lára
authors.initials: L
authors.lastname: Hannesdóttir
authors.forename: Nina
authors.initials: N
authors.lastname: Daschil
authors.forename: Sonja
authors.initials: S
authors.lastname: Philipp
authors.forename: Piotr
authors.initials: P
authors.lastname: Tymoszuk
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Müller-Holzner
authors.forename: Günter
authors.initials: G
authors.lastname: Klima
authors.forename: Irmgard
authors.initials: I
authors.lastname: Verdorfer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Doppler
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006107:Granulosa Cells / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000172:deficiency* / Q000235:genetics; D013724:Teratoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013799:Theca Cells / Q000378:metabolism / Q000473:pathology; D046509:Tissue Culture Techniques
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse