The role of the type I insulin-like growth factor receptor in lung tumorigenesis
The type I insulin-like growth factor receptor (IGF-IR) has been observed to be overexpressed in the majority lung cancer cell lines and human lung tumor biopsies. Two doxycycline-inducible transgenic mouse models in which the IGF-IR was overexpressed in either the Clara cells or the type II alveolar cells of the lung were used in this study. It was discovered that mice overexpressing IGF-IR in the type II alveolar cells of the lung developed a greater tumor burden than mice overexpressing IGF-IR in the Clara cells. Tumors were also found to develop more quickly in mice overexpressing IGF-IR in the type II alveolar cells ofthe lung that were treated with doxycycline in utero in comparison to postnatally, however this finding was not statistically significant. The interaction between nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and the IGF-IR was then investigated in this study, and NNK was injected into both of the transgenic mouse models. No significant differences in tumor development were found between transgenic mice that received NNK injections and those that did not. However, endogenous murine IGF-IR was found to be expressed at high levels in the tumors that developed in the wildtype NNK injected mice, providing evidence that the IGF-IR may playa significant role in mediating the carcinogenic effects of NNK.