{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T22:25:42Z","timestamp":1767651942681},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,5,19]],"date-time":"2003-05-19T00:00:00Z","timestamp":1053302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tumor angiogenesis is governed by a complex balance of positive and negative angiogenic factors. Development of chemically\u2010induced mouse skin tumors appears to be highly dependent on an early burst of neovascularization. We have previously shown that Ha\u2010<jats:italic>ras<\/jats:italic>\u2013driven vascular endothelial growth factor (VEGF) expression plays a pivotal role in this process. However, the status of other critical positive and negative angiogenic factors throughout skin tumorigenesis has not been studied to the same extent. In the present study, we show that another VEGF family member, placenta growth factor (PlGF), was highly upregulated at all tumor stages in a <jats:italic>ras<\/jats:italic>\u2010dependent manner. The study of angiopoietin\u20101 (Ang\u20101) and angiopoietin\u20102 (Ang\u20102), ligands of receptor tyrosine kinase 2 (Tie\u20102), showed that while stroma\u2013derived Ang\u20102 was increased, epidermal Ang\u20101 expression was completely abolished at early papilloma formation. Studies using epidermal tumor cell lines suggest that the disappearance of Ang\u20101 also depends on <jats:italic>ras<\/jats:italic> activation, extending the plethora of events controlled by this oncogene in mouse skin carcinogenesis. Our results indicated that tumor development occurred in a strong angiogenesis\u2010prone scenario in which PlGF and Ang\u20102 acted cooperatively with VEGF, whereas the negative or stabilizing effect of Ang\u20101 was abrogated. A time\u2010course sequence of expression of angiogenic factors expressed throughout tumor growth, as well as the identification of key signaling molecules triggering the angiogenic response, may contribute to the development and testing of antiangiogenic therapeutic strategies with this in vivo tumor model. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.10126","type":"journal-article","created":{"date-parts":[[2003,5,21]],"date-time":"2003-05-21T10:02:10Z","timestamp":1053511330000},"page":"83-90","source":"Crossref","is-referenced-by-count":34,"title":["Modulation of the angiogenesis response through Ha\u2010<i>ras<\/i> control, placenta growth factor, and angiopoietin expression in mouse skin carcinogenesis"],"prefix":"10.1002","volume":"37","author":[{"given":"Fernando","family":"Larcher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Franco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Bolontrade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Rodriguez\u2010Puebla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Llanos","family":"Casanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Yancopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 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