Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction (original) (raw)

Nature Genetics volume 21, pages 182–186 (1999)Cite this article

Abstract

The lats gene has been identified as a tumour suppressor in Drosophila melanogaster using mosaic screens1. Mosaic flies carrying somatic cells that are mutant for lats develop large tumours in many organs1,2. The human LATS1 homologue rescues embryonic lethality and inhibits tumour growth in lats mutant flies, demonstrating the functional conservation of this gene3. Biochemical and genetic analyses have revealed that LATS1 functions as a negative regulator of CDC2 (ref. 3). These data suggest that mammalian LATS1 may have a role in tumorigenesis. To elucidate the function of mammalian LATS1, we have generated Lats1 –/– mice. Lats1 –/– animals exhibit a lack of mammary gland development, infertility and growth retardation. Accompanying these defects are hyperplastic changes in the pituitary and decreased serum hormone levels. The reproductive hormone defects of Lats1 –/– mice are reminiscent of isolated LH–hypogonadotropic hypogonadism and corpus luteum insufficiency in humans. Furthermore, Lats1 –/– mice develop soft–tissue sarcomas and ovarian stromal cell tumours and are highly sensitive to carcinogenic treatments. Our data demonstrate a role for Lats1 in mammalian tumorigenesis and specific endocrine dysfunction.

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Acknowledgements

We thank Y. Zhuang and G. Terwilliger for advice; members of the Xu lab for invaluable comments; and S. Shi, T. Potselueva, W. Yu and K. Sepanek for assistance. M.S.J. is a MSTP student and also supported by an Anna Fuller Scholarship. W.T. was an Anna Fuller Fellow. This work is supported in part by grants from NIH (R01CA69408) and the Lucille P. Markey Charitable Trust.

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Author notes

  1. Maie A R St John and Wufan Tao: These authors contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536–0812 , Connecticut, USA
    Maie A R St John, Wufan Tao, Xiaolan Fei, Royd Fukumoto & Tian Xu
  2. Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536–0812, Connecticut, USA
    Wufan Tao, Xiaolan Fei, Royd Fukumoto, James McGrath & Tian Xu
  3. Department of Cell Biology, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536–0812 , Connecticut, USA
    Maie A R St John
  4. Department of Pathology, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536–0812 , Connecticut, USA
    Maria Luisa Carcangiu
  5. Section of Comparative Medicine, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536–0812 , Connecticut, USA
    David G Brownstein
  6. National Hormone and Pituitary Program, Harbor–UCLA Medical Center, 1000 West Carson St., Torrance , 90509, California, USA
    Albert F Parlow

Authors

  1. Maie A R St John
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  2. Wufan Tao
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  3. Xiaolan Fei
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  4. Royd Fukumoto
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  5. Maria Luisa Carcangiu
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  6. David G Brownstein
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  7. Albert F Parlow
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  8. James McGrath
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  9. Tian Xu
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Corresponding author

Correspondence toTian Xu.

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St John, M., Tao, W., Fei, X. et al. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction.Nat Genet 21, 182–186 (1999). https://doi.org/10.1038/5965

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