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

在肺癌中诱导肿瘤分化的研究，不仅为明确恶性转化的机制提供了可能，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克隆抗体，并试图鉴定其表位的c-DNA。其中一种抗体KM43-2可以改变人小细胞肺癌细胞系SBC- 1的形态，抑制细胞运动。我们发现该抗体识别两种跨膜蛋白，分子量分别为60K和71K。基因克隆证实其表位为560个碱基，并将其命名为分化诱导蛋白（DIP）。然而，Western blot测定的分子量与基因克隆得到的cDNA碱基数存在较大差异。此外，将该cDNA转染到SBC- I中，在生物学功能和形态学上都没有引起显著的变化。这些发现的部分原因可能是由于DIP基因的全cDNA鉴定不完整。我们试图用抗体亲和柱鉴定其蛋白的整个结构，但迄今为止还没有成功地用这种方法鉴定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 .