Expression of hedgehog signaling molecules in lung cancer.

Abnormal hyperactivation of the hedgehog (Hh) pathway has been reported in many types of human cancers, including lung cancer. However, most reports are based on studies of fewer than three Hh target genes and the data vary between different studies. In the present report, we have determined the expression levels of several important components of the Hh pathway in lung cancers by using RT-PCR, in situ hybridization and immunohistochemistry. These molecules include Smoothened (SMO), Rab23, the downstream target platelet-derived growth factor receptor alpha (PDGFRα), hedgehog interacting protein (HIP) and hepatocyte nuclear factor 3-beta (HNF3β). Our data show that some components of the hedgehog pathway, such as SMO, Rab23 and PDGFRα are expressed in many lung cancer specimens, although other hedgehog target genes are infrequently detected in lung cancer. Loss of HIP expression was found in several cases of lung cancers. Our study indicates that there might be some additional mechanisms involved in the hyperactivation of the Hh pathway. Thus, we suggest that lung cancer with heterogeneous tumor type harboring Hh signaling activation may have some novel and different regulatory mechanisms.