Differences in the regulation of Thrombospondin-1 expression between epithelial cells and fibroblasts

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Rodriguez, Roberto Karlo

Advisor dc:contributor.advisor

• Randolph Watnick and Tyler Jacks.

• Biology.

Statement dc:rights

• 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.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/38992

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38992