Analysis of Differentiation Inducing Protein (DIP) Gene in Small Cell Lung Cancer and Its Expression in Lung Cancer.

对肺癌肿瘤诱导分化的研究不仅为明确肺癌的恶性转化机制提供了可能，也为开发新的抗肿瘤药物提供了可能。在这方面，为了阐明与肿瘤分化相关的分子，我们一直在生产能够诱导肿瘤分化的单抗，并一直试图鉴定其表位的c-DNA。其中一种抗体KM43-2改变了人类小细胞肺癌细胞系SBC-1的形态，并抑制了细胞的运动。我们发现该抗体识别两种跨膜蛋白，分子量分别为60K和71K。基因克隆证实编码其表位的基因全长为560个碱基，命名为分化诱导蛋白(DIP)。然而，蛋白质印迹法测得的相对分子质量与基因克隆测得的碱基数有很大差异。此外，将该基因导入SBC-I细胞后，其生物学功能和细胞形态均未发生明显变化。这些发现可能部分归因于对DIP基因全长的不完全鉴定。我们曾尝试用抗体亲和层析柱鉴定其蛋白的完整结构，但至今仍未成功地用该方法鉴定DIP基因。另一方面，这些结果可能部分是因为跨膜蛋白的糖链可能主要调节DIP的功能。考虑到这些原因，我们正在对DIP进行进一步的研究，以确定其基因并阐明其确切的生物学作用。

Studies on induction of tumor differentiation in lung cancer may present the possibility of not only identifying the mechanism of malignant transformation, but also lead to development of new anti-tumor drugs. In this regard, to elucidate the molecules associated with tumor differentiation, we have been producing monoclonal antibodies which are able to induce tumor differentiation, and have been trying to identify the c-DNA of their epitope. One such antibody, KM43-2, changes the morphology of SBC- 1 , a human small cell lung cancer cell line, and inhibits the cell motility. We revealed that this antibody recognizes two transmembrane proteins, of 60K and 71K molecular weight, respectively. Genetic cloning demonstrated that the cDNA coding its epitope was of 560 base, and we named it differentiation inducing protein (DIP). However, there are substantial differences between the molecular weight measured by Western blot and base number of cDNA from genetic cloning. In addition, transfection of this cDNA into SBC- I did not cause a significant change in either biological function or morphology. These findings might be partly due to incomplete identification of the whole cDNA of the DIP gene. We tried to identify the entire structure of its protein using antibody affinity column, but to date have not succeed in identification of the DIP gene using this method. On the other hand, these results might be partly because the sugar chain of the transmembrane protein might chiefly regulate the function of DIP. Considering these reasons, we are performing further studies on DIP to identify its gene and to clarify its precise biological roles .