Does Growth Hormone Cause Cancer?

P. J. Jenkins; A. Mukherjee; S. M. Shalet


Clin Endocrinol. 2006;64(2):115-121. 

In This Article

Animal Studies

More compelling evidence comes from animal studies that have involved manipulation of the GH/IGF-1 axis. Transgenic mice for both human GH and agonists for the IGF-1 receptor show an increased incidence of breast tumour development.[5,6] In contrast, lit/lit mice, which are characterized by a nonfunctioning GHRH receptor and thus serum GH and IGF-1 levels approximately 10% that of normal, show almost complete inhibition of growth of transplanted human breast cancer cells.[7] In addition, serum from lit/lit mice was less mitogenic to breast cancer cells in vitro than control serum, a difference abolished by the addition of IGF-1 to the lit/lit serum. Antibodies against the IGF-1 receptor block the in vivo growth of subcutaneous breast cancers transplanted into nude mice,[8] and more recent studies have demonstrated mice transfected with the growth hormone receptor antagonist to have a significantly reduced incidence of mammary carcinogenesis.[9] Mechanisms for selective knockout of the hepatic IGF-1 gene, which results in a marked reduction of circulating IGF-1 levels, have recently been developed.[10,11] Not only do these animals provide an elegant model with which to explore the relative contributions of endocrine and paracrine/autocrine IGF-1 effects, but the reduction in circulating IGF-1 is associated with a marked delay in the onset of chemically and genetically induced mammary and colonic tumours.[10,11] It must be remembered, however, that all these models involve variations in IGF-1 levels that are large compared with the more subtle variations in IGF-1 physiology that exists between humans.

In addition to its proliferative and antiapoptotic actions, IGF-I exerts influential effects on the metastatic potential of cancers.[10,12] This is an area of considerable interest in the development of potential chemotherapeutic strategies, as it is the metastatic spread that is ultimately responsible for the mortality of most cancers. Powerful evidence in support of this role was recently demonstrated by Sachdev et al., utilizing the LCC6 metastatic breast cancer cell line.[13] Cells were transfected with a truncated IGF-1 receptor that effectively silenced the expression of the endogenous IGF-1 receptor and thus inhibited IGF-1 mediated signalling. The transfected cells were transplanted into nude mice and subsequent metastatic spread assessed. After 2 months, multiple pulmonary metastases were present in animals transplanted with wild-type cells, whereas these were completely absent in those animals transplanted with the transfected cells.