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Transforming Growth Factor B Regulation of Tumor Progression in Metastatic Cancer

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Annual rept. 1 Jun 2000-31 May 2001

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Osteoclast-mediated bone degradation is a debilitating result of metastasis to bone. During the metastatic tumor development, osteoclasts differentiate in the presence of high concentrations of transforming growth factor beta TGF-Beta. Our data support the hypothesis that TGF-Beta is a survival factor for TGF-Beta-induced osteoclasts. We had planned to test our hypothesis by pursuing the following two objectives 1 Determine the effects of TGF-Beta on tumor development in bone in vivo, and 2 Determine the role of TGF-Beta signal transduction in TGF-Beta influences on mouse osteoclast-like cell survival. Objective 1 has proven difficult to achieve as the reagents that were planned for blocking activity in vivo were rapidly degraded in the animals. To circumvent this problem we generated cells that express either the dominant interfering or the constitutively active TGF-Beta receptor. These have been injected in both the heart and bone to achieve the aims of this objective. The goal of objective 2 have been difficult to achieve the transfection technique induced apoptosis. We are currently establishing the adenoviral transfection technique in the laboratory to circumvent this difficulty. Overall, given the technological obstacles, we have made very good progress on the objectives of this proposal.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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