Does Growth Hormone Cause Cancer?

Does Growth Hormone Cause Cancer?

Actions of IGF-1 in Relation to Cancer

IGF-1 exerts powerful effects on each of the key stages of cancer development and behaviour: cellular proliferation and apoptosis, angiogenesis and metastasis, and more recently, development of resistance to chemotherapeutic agents. It is a potent proliferative agent affecting almost every cell type, an effect predominantly, although not exclusively, mediated via the mitogen-activated protein (MAP) kinase signalling pathway. In addition to these proliferative actions, IGF-1 is also a powerful antiapoptotic agent influencing the apoptotic responses to a variety of agents of numerous cell types. These antiapoptotic actions tend to be mediated via the PI-3 kinase pathway, although this is again not exclusive, and there is considerable cross-talk between the two predominant signalling pathways.

The end results of these opposing effects of IGF-1 may be several-fold. First, there is increased proliferation and thus epithelial cell turnover within tissues. Second, the antiapoptotic effects cause an imbalance in the usual tight control between proliferation and cell death and result in hyperproliferation. This is the first stage in the development of many cancers and has been particularly well demonstrated in colorectal tumorigenesis in which it precedes the formation of colonic adenomas. Third, such an imbalance between cell proliferation and death would favour, even slightly, survival of stem cells that had undergone early genetic 'hits'. This would increase the pool of damaged cells available for second and subsequent hits. Higher levels of IGF-1 would be expected to activate survival pathways that would make programmed cell death of damaged cells slightly less probable. When applied overall to a large number of 'at risk' cells over many years, even a small influence in favour of survival of such cells could accelerate carcinogenesis, although not initiate cancer development per se.