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Randolph Watnick and Tyler Jacks. Rodriguez, Roberto Karlo Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Department of Biology 2007-09-28T13:28:34Z 2007-09-28T13:28:34Z 2007 2007 http://hdl.handle.net/1721.1/38992 166421348 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2007. Includes bibliographical references (p. 131-157). 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. by Roberto Karlo Rodriguez. Ph.D. 157 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Biology. Differences in the regulation of Thrombospondin-1 expression between epithelial cells and fibroblasts Differences in the regulation of Tsp-1 expression between epithelial cells and fibroblasts Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="0b7141d1-5141-4d3e-bef4-2d9ca8e5f41e"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Differences in the regulation of Thrombospondin-1 expression between epithelial cells and fibroblasts</Title> <Subtitle>Differences in the regulation of Tsp-1 expression between epithelial cells and fibroblasts</Subtitle> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2007</PublicationDate> <Authors> <Author> <DisplayName>Rodriguez, Roberto Karlo</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biology.</Keyword> <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.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>