Signal transmission of carcinogenesis and tumorigenesis and formation of specific metabolic pathway in tumor cells.

以前，我们发现II型己糖激酶的转录水平在恶性肿瘤细胞中是显著的。然而，引起肿瘤细胞中II型己糖激酶转录水平如此剧烈变化的分子机制仍然未知。因此，在本研究中，我们试图了解该基因在肿瘤细胞中的表达是如何调节的。我们得到了如下结果：1.我们首先探索了在何种条件下II型己糖激酶的表达显著。结果，当AH13O细胞在大鼠腹腔中生长时，II型己糖激酶的转录水平显著。然而，当该细胞系在培养皿中生长时，II型己糖激酶的转录水平显著低于用腹水细胞观察到的水平。这些结果表明，随着培养条件的改变，II型己糖激酶的转录水平会发生变化.为了了解这种显着的变化是如何引起的，我们检查了可能涉及缺氧和血清刺激。结果表明，血清刺激可显著提高II型己糖激酶的基因表达，提示肿瘤细胞生长条件的改变可导致糖代谢途径的改变，而这种改变主要由血清反应因子介导。

Previously, we found that the transcript level of type II hexokinase was remarkable in malignant tumor cells. However, the molecular mechanisms which cause such drastic changes in the transcript level of type II hexokinase in tumor cells is still unknown. Thus, in this study, we tried to understand how the expression of this gene is regulated in tumor cells. We obtained following results.1. We first explored under which condition the expression of type II hexokinase is remarkable. As a result, transcript level of type II hexokinase was remarkable when AH13O cells were grown in an abdominal cavity of rats. However, when this cell line was grown in culture dishes, the transcript level of type II hexokinase was remarkably lower than that observed with ascites cells. These results indicate that the transcript level of type II hexokinase could be changed accompanied by changes in culture conditions.2. To understand how such remarkable change is caused, we examined possible involvement of hypoxia and serum stimulation. As a result, gene expression of type II hexokinase was remarkably elevated by serum stimulation.Based on these results, we concluded that the metabolic pathway of sugar in tumor cells could be changed accompanied by changes in their growth conditions and that this change is mainly mediated by serum responsive factor.