Roles for insulin-like growth factor-1 in mediating the anti-carcinogenic effects of caloric restriction.

摘要: This paper focuses on the role of insulin-like growth factor-1 (IGF-1) and its associated regulatory apparatus as a key endocrine, autocrine, paracrine signalling system involved in mediating anti-carcinogenic activity dietary restriction. Literature is reviewed showing that inhibitory action restriction carcinogenesis global pervasive--it effective several laboratory species, for variety tumor types, both spontaneous tumors caused by different types tumor-inducing agents. Evidence presented IGF-1 pathway responds appropriately to nutritional interventions including diet Recent evidence points an obligatory receptor establishment maintenance transformed phenotype reveals concert with binding protein 3 p53 autocrine/paracrine signaling pathways adaptive responses environmental stimuli. Considered together these works show uniquely poised influence cellular transformation leading malignant modulating balance proliferation cell death (apoptosis) precancerous cancerous cells influencing metastasis nascent tumors. We evaluated hypotheses directly using animal models mononuclear leukemia, bladder transitional carcinogenesis, breast cancer. Our studies demonstrate manipulation level through intervention influences metastasis. Upregulation this demonstrated increased stimulates proliferation, progression Conversely, downregulation vivo consequence results antitumorigenic activity. found functional disruption IGF-1R markedly cancer nude mice suppressing adhesion, invasion, lung, lymph nodes, vessels. Epidemiological observations clinical oncology support involvement anticarcinogenesis. leads hypothesis factors such which regulate body size composition may be related human incidence or prognosis. Additional understanding interactions other will advance our ability develop new towards decreased risk humans.