Chong I W, Lin S R, Lin M S, Huang M S, Tsai M S, Hwang J J
Department of Internal Medicine, Kaohsiung Medical College, Taiwan ROC.
J Formos Med Assoc. 1997 Aug;96(8):579-85.
Transforming growth factor-alpha (TGF-alpha), a member of the epidermal growth factor (EGF) family that binds to the EGF receptor (EGFR), is thought to function in an autocrine manner in non-small cell lung cancers (NSCLC). Heparin-binding EGF-like growth factor (HB-EGF), a novel member of the EGF family, also binds to EGFR. To compare the expression 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 human NSCLC and normal lung tissues by Northern hybridization, reverse transcription-polymerase chain reaction (RT-PCR), and in situ hybridization. A total of eight specimens (paired tumor tissue and normal lung tissue) were harvested from four patients who underwent resection of primary resectable NSCLC. HB-EGF was not expressed in either tumor tissue or normal lung tissue, while EGFR and TGF-alpha were expressed in all samples. TGF-alpha was overexpressed in all tumor tissue samples by several hundred-fold, while the expression of EGFR was not significantly different in tumor tissue and normal lung tissue. There was no correlation between the expression of TGF-alpha and EGFR. In situ hybridization showed that TGF-alpha mRNA was localized mainly in the cancer cells of tumor tissues and in the macrophages of alveoli in normal lung tissue. Our results showed that HB-EGF plays no role in the growth of NSCLC, and that there was no significant overexpression of EGFR in tumor tissue. TGF-alpha may play a major role in the growth of NSCLC. This supports a new direction in rational NSCLC treatment.
转化生长因子-α（TGF-α）是表皮生长因子（EGF）家族的成员，可与EGF受体（EGFR）结合，被认为在非小细胞肺癌（NSCLC）中以自分泌方式发挥作用。肝素结合表皮生长因子样生长因子（HB-EGF）是EGF家族的新成员，也可与EGFR结合。为比较HB-EGF、TGF-α和EGFR基因在NSCLC和正常肺组织中的表达情况，我们通过Northern杂交、逆转录-聚合酶链反应（RT-PCR）和原位杂交技术，检测了人NSCLC及正常肺组织中这些基因的信使核糖核酸（mRNA）水平。从4例接受原发性可切除NSCLC切除术的患者中，共获取了8份标本（配对的肿瘤组织和正常肺组织）。HB-EGF在肿瘤组织和正常肺组织中均未表达，而EGFR和TGF-α在所有样本中均有表达。TGF-α在所有肿瘤组织样本中均有数百倍的过表达，而EGFR在肿瘤组织和正常肺组织中的表达无显著差异。TGF-α与EGFR的表达之间无相关性。原位杂交显示，TGF-α mRNA主要定位于肿瘤组织的癌细胞及正常肺组织肺泡的巨噬细胞中。我们的结果表明，HB-EGF在NSCLC生长中不起作用，肿瘤组织中EGFR无明显过表达。TGF-α可能在NSCLC生长中起主要作用。这为NSCLC的合理治疗提供了新方向。
