Differences in the regulation of Thrombospondin-1 expression between epithelial cells and fibroblasts
Name
166421348-MIT.pdf
Description
Full printable version
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8.82 MB
Format
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Checksum (MD5)
698d1c385819134082238c417772f8b8
Author(s)
Rodriguez, Roberto Karlo
Advisor(s)
Randolph Watnick and Tyler Jacks.
Alternative Title
Differences in the regulation of Tsp-1 expression between epithelial cells and fibroblasts
Date Issued
2007
Publisher
Massachusetts Institute of Technology
Abstract
Induction of angiogenesis is a critical and rate-limiting step in the progression of cancer. It is widely acknowledged that this induction requires the concomitant stimulation of pro-angiogenic and repression of anti-angiogenic proteins. It has been demonstrated that in human epithelial cells repression of the angiogenesis inhibitor Thrombospondin-1 (Tsp-1) requires stimulation of Myc in combination with hyper-physiologic levels of oncogenic Ras. This work demonstrates that in human mammary epithelial cells, repression of Tsp-1 requires the activation of Myc by a Ras-induced pathway that activates the MAPK p38. This work also demonstrates that repression of Tsp-1 in human fibroblasts requires the combined inhibition of the tumor suppressors p53 and pRb. These results suggest that the molecular requirements for the induction of angiogenesis differ significantly between carcinomas and sarcomas.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2007.
Includes bibliographical references (p. 131-157).
Subjects
Biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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