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

对肺癌细胞诱导分化的研究，不仅可以揭示肺癌细胞恶性转化的机制，而且有助于开发新的抗肿瘤药物。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，并一直在试图鉴定其表位的c-DNA。一种这样的抗体，KM 43 -2，改变SBC- 1（一种人小细胞肺癌细胞系）的形态，并抑制细胞运动。我们发现，这种抗体识别两个跨膜蛋白，60 K和71 K的分子量，分别。基因克隆表明，编码其表位的cDNA为560个碱基，我们将其命名为分化诱导蛋白（DIP）。然而，通过Western blot测定的分子量与基因克隆的cDNA的碱基数之间存在实质性差异。此外，将该cDNA转染到SBC-1中不会引起生物学功能或形态学的显著变化。这些结果可能部分是由于DIP基因的完整cDNA鉴定不完全。我们试图用抗体亲和柱鉴定其蛋白质的整个结构，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 .