Int. J. Dev. Biol. 56: 279 - 283 (2012)

https://doi.org/10.1387/ijdb.113397lh

Vol 56, Issue 4

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

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.

Keywords

teratoma, ovary, STAT1, folliculogenesis