Type I insulin-like growth factor receptor induces pulmonary tumorigenesis.

Despite the type I insulin-like growth factor receptor (IGF-IR) being highly expressed in more than 80% of human lung tumors, a transgenic model of IGF-IR overexpression in the lung has not been created. We produced two novel transgenic mouse models in which IGF-IR is overexpressed in either lung type II alveolar cells (surfactant protein C [SPC]-IGFIR) or Clara cells (CCSP-IGFIR) in a doxycycline-inducible manner. Overexpression of IGF-IR in either cell type caused multifocal adenomatous alveolar hyperplasia with papillary and solid adenomas.

IGF-II induces CREB phosphorylation and cell survival in human lung cancer cells.

We have previously shown that lung tumors arising in MMTV-IGF-II transgenic mice displayed elevated levels of phosphorylated cAMP response element binding protein (CREB). To investigate the role that insulin-like growth factor II (IGF-II) and CREB play in human lung tumorigenesis, A549 and NCI-H358 cells were examined. In these cell lines, IGF-II administration enhances human tumor cell survival and CREB phosphorylation.

Use of a transgenic mouse model to identify markers of human lung tumors.

Lung cancer remains the leading cause of cancer related deaths worldwide. Despite advances in detection technologies, most patients diagnosed with lung cancer already harbor metastatic lesions. Because early detection is one of the primary determinants of patient outcome, a transgenic mouse model of lung cancer was utilized to identify markers of early lung tumors in humans.