LAPTM4B在宫颈癌血管生成和侵袭转移中的分子机制研究

Studies have shown that Lysosome-associated protein transmembrane 4 beta (LAPTM4B) has important roles in multiple biological processes during cancer development and progression, including malignant transformation, apoptosis, invasion and metastasis through its involvement in several oncogenic signal transduction pathways. For the first time our previous findings have revealed that the LAPTM4B gene polymorphisms may play an important role in genetic susceptibility to cervical cancer in the Chinese population. In addition, we found that the overexpression of LAPTM4B in cervical carcinoma was significantly associated with FIGO stage and lymph node metastasis，but the real mechanism needs further research. Based on these previous findings, we supposed that LAPTM4B could enhance tumor angiogenesis and promote the invasion of cervical carcinoma. To the best of our knowledge, this is the first study investigating the association between LAPTM4B and tumor angiogenesis. In this study, shRNA eukaryotic expressing vector of human LAPTM4B with RNA interference approach was constructed and transfected into cervical cancer cell lines. The purpose of the present study was to investigate the role of LAPTM4B in angiogenesis and the invasion mechanism of LAPTM4B expression in cervical carcinoma. This study will provide some theoretical bases for tumor targeting and cancer therapy.

溶酶体相关4次跨膜蛋白质β(LAPTM4B)基因与肿瘤发生、侵袭转移、细胞周期调控均有密切关系，是很有前景的肿瘤治疗靶点。申请者前期在国际上首次发现LAPTM4B基因多态性与宫颈癌易感性相关，而且LAPTM4B表达与宫颈癌临床分期、淋巴结转移等病理学参数密切相关，但其作用机制还有待进一步探讨。为此，我们率先提出假说：LAPTM4B基因参与肿瘤血管生成，从而导致恶性肿瘤的发生。为了验证这一假说，我们将结合RNA干扰技术，通过构建LAPTM4B基因真核表达载体，建立稳定转染反义表达LAPTM4B基因的人宫颈癌细胞株，分别进行体外和体内实验，探讨LAPTM4B基因表达与肿瘤血管生成、侵袭转移相关因子VEGF、MMP-2等的相关性，分析LAPTM4B基因对肿瘤生物学特性、体内致瘤性和微血管密度的影响，揭示LAPTM4B在宫颈癌血管形成、侵袭转移过程中的分子机制，为探索肿瘤靶向基因治疗提供理论依据。

溶酶体相关4次跨膜蛋白质β (LAPTM4B) 基因与肿瘤发生、侵袭转移、细胞周期调控均有密切关系，是很有前景的肿瘤治疗靶点。申请者在前期工作的基础上，国际上率先提出并验证了以下假说：LAPTM4B基因参与肿瘤血管生成，从而导致恶性肿瘤的发生。我们结合RNA干扰技术，通过构建LAPTM4B基因真核表达载体，建立稳定转染反义表达LAPTM4B基因的人宫颈癌细胞株，通过体外实验，探讨LAPTM4B基因表达与肿瘤血管生成、侵袭转移相关因子的相关性，分析LAPTM4B基因对肿瘤生物学特性和血管生成的影响，揭示了LAPTM4B基因在宫颈癌血管形成、侵袭转移过程中的分子机制，为探索肿瘤靶向基因治疗提供理论依据。本项目已获得了一系列研究成果，已发表SCI收录论文3篇。