Is oncogene addiction angiogenesis-dependent?
Does an activated oncogene that initiates tumor growth need to remain activated to maintain the cancer phenotype? This question has been answered affirmatively by experiments in which doxycycline-regulated oncogene activation induces growth of large tumors that regress completely upon oncogene inactivation--a phenomenon called oncogene addiction. We assemble here the evidence that oncogene addiction is angiogenesis-dependent. Although activated oncogenes increase tumor cell proliferation and decrease their apoptosis, these activities are not sufficient to expand tumor mass beyond a microscopic size. Oncogenes must also induce tumor angiogenesis for expansion of tumor mass. We propose experiments to validate the "endothelial centric" hypothesis of oncogene addiction.
Folkman
J
J
The Vascular Biology Program, Department of Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Ryeom
S
S
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004318:Doxycycline / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics*; D009857:Oncogenes / Q000187:drug effects; D019700:Thrombospondin 1 / Q000378:metabolism
D019700:Thrombospondin 1; D004318:Doxycycline