HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA IN HUMAN NONSMALL CELL LUNG CANCERS

Transforming growth factor-alpha (TGF-alpha), a member of the epiderma l growth factor (EGF) family that binds to the EGF receptor (EGFR), is thought to function in an autocrine manner in non-small cell lung can cers (NSCLC). Heparin-binding EGF-like growth factor (HB-EGF), a novel member of the EGF family, also binds to EGFR. To compare the expressi on of HB-EGF, TGF-alpha and EGFR genes in NSCLC and normal lung tissue , we measured the levels of messenger RNA (mRNA) for these genes in hu man NSCLC and normal lung tissues by Northern hybridization, reverse t ranscription-polymerase chain reaction (RT-PCR), and in situ hybridiza tion. A total of eight specimens (paired tumor tissue and normal lung tissue) were harvested from four patients who underwent resection of p rimary resectable NSCLC. HB-EGF was not expressed in either tumor tiss ue or normal lung tissue, while EGFR and TGF-alpha were expressed in a ll samples. TGF-alpha was overexpressed in all tumor tissue samples by several hundred-fold, while the expression of EGFR was not significan tly different in tumor tissue and normal lung tissue. There was no cor relation between the expression of TGF-alpha and EGFR In situ hybridiz ation showed that TGF-alpha mRNA was localized mainly in the cancer ce lls of tumor tissues and in the macrophages of alveoli in normal lung tissue. Our results showed chat HB-EGF plays no role in the growth of NSCLC, and that there was no significant overexpression of EGFR in tum or tissue. TCF-alpha may play a major role in the growth of NSCLC. Thi s supports a new direction in rational NSCLC treatment.