Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis. Export

@article{citeulike:913143, abstract = {Tumor angiogenesis is postulated to be regulated by the balance between pro- and anti-angiogenic factors. We demonstrate that the critical step in establishing the angiogenic capability of human cells is the repression of the critical anti-angiogenic factor, thrombospondin-1 (Tsp-1). This repression is essential for tumor formation by mammary epithelial cells and kidney cells engineered to express SV40 early region proteins, hTERT, and H-RasV12. We have uncovered the signaling pathway leading from Ras to Tsp-1 repression. Ras induces the sequential activation of PI3 kinase, Rho, and ROCK, leading to activation of Myc through phosphorylation; phosphorylation of Myc via this mechanism enables it to repress Tsp-1 expression. We thus describe a novel mechanism by which the cooperative activity of the oncogenes, ras and myc, leads directly to angiogenesis and tumor formation.}, address = {Whitehead Institute for Biomedical Research, Cambridge, MA 01242, USA.}, author = {Watnick, R. S. and Cheng, Y. N. and Rangarajan, A. and Ince, T. A. and Weinberg, R. A.}, citeulike-article-id = {913143}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/12676581}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=12676581}, issn = {1535-6108}, journal = {Cancer Cell}, keywords = {angiogenesis, c-myc, k-ras, tsp1}, month = {March}, number = {3}, pages = {219--231}, posted-at = {2006-10-26 10:53:41}, priority = {2}, title = {Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12676581}, volume = {3}, year = {2003} }

TY - JOUR ID - citeulike:913143 L3 - citeulike-article-id:913143 N2 - Tumor angiogenesis is postulated to be regulated by the balance between pro- and anti-angiogenic factors. We demonstrate that the critical step in establishing the angiogenic capability of human cells is the repression of the critical anti-angiogenic factor, thrombospondin-1 (Tsp-1). This repression is essential for tumor formation by mammary epithelial cells and kidney cells engineered to express SV40 early region proteins, hTERT, and H-RasV12. We have uncovered the signaling pathway leading from Ras to Tsp-1 repression. Ras induces the sequential activation of PI3 kinase, Rho, and ROCK, leading to activation of Myc through phosphorylation; phosphorylation of Myc via this mechanism enables it to repress Tsp-1 expression. We thus describe a novel mechanism by which the cooperative activity of the oncogenes, ras and myc, leads directly to angiogenesis and tumor formation. IS - 3 JF - Cancer Cell SN - 1535-6108 AD - Whitehead Institute for Biomedical Research, Cambridge, MA 01242, USA. EP - 231 TI - Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis. VL - 3 SP - 219 KW - angiogenesis KW - c-myc KW - k-ras KW - tsp1 AU - Watnick, RS AU - Cheng, YN AU - Rangarajan, A AU - Ince, TA AU - Weinberg, RA PY - 2003/03// UR - http://view.ncbi.nlm.nih.gov/pubmed/12676581 ER -