Estrogen Enhances whereas Tamoxifen Retards Development of Tsc Mouse Liver Hemangioma: A Tumor Related to Renal Angiomyolipoma and Pulmonary Lymphangioleiomyomatosis

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  • Nisreen El-Hashemite
    Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
  • Victoria Walker
    Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
  • David J. Kwiatkowski
    Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts

抄録

<jats:title>Abstract</jats:title><jats:p>Pulmonary lymphangioleiomyomatosis and abdominal angiomyolipoma are related lesions for which there is no authentic animal model. Both of these proliferative lesions occur in sporadic patients, and at much higher frequency in patients with tuberous sclerosis, which is due to mutations in the TSC1 and TSC2 genes. Tsc1+/− and Tsc2+/− mice frequently develop liver hemangioma. We found that the Tsc mouse liver hemangioma are composed predominantly of endothelial cells but with a smooth muscle component, and express HMB45 antigen, estrogen receptor, and progesterone receptor, similar to lymphangioleiomyomatosis and angiomyolipoma. Estrogen treatment significantly accelerated the development of liver hemangioma in Tsc1+/− female mice, with 91% having liver hemangioma and 55% having severe lesions by 7 months of age. Similarly, an increased frequency and severity of liver hemangiomas was seen in Tsc1+/− males treated with estrogen. In contrast, tamoxifen treatment for 9 months significantly reduced the frequency and severity of hemangiomas in Tsc1+/− female mice. In addition, estrogen treatment significantly increased serum vascular endothelial growth factor levels in Tsc1+/− mice, whereas tamoxifen reduced vascular endothelial growth factor levels. These mouse model observations indicate the importance of estrogen signaling in vivo for the growth of tuberous sclerosis lesions, suggesting the possible benefits of tamoxifen therapy for the treatment of angiomyolipoma and lymphangioleiomyomatosis.</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 65 (6), 2474-2481, 2005-03-15

    American Association for Cancer Research (AACR)

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