Is Oncogene Addiction Angiogenesis-dependent?

Abstract

Does an activated oncogene that initiates tumor growth need to remain activated to maintain the cancer phenotype? This questionhas been answered affirmatively by experiments in which doxycycline-regulated oncogene activation induces growth oflarge tumors that regress completely upon oncogene inactivation—a phenomenon called oncogene addiction. We assemblehere the evidence that oncogene addiction is angiogenesis-dependent. Although activated oncogenes increase tumor cell proliferationand 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 "endothelialcentric" hypothesis of oncogene addiction.