TMPRSS4与乳腺癌发生及侵袭转移相关性的研究

Type II transmembrane serine proteases (TTSPs), which are directly anchored to the cell membranes, have been recognized as a new subfamily of serine proteases, and involed in epithelial-mesenchymal transition(EMT),tumor invasion, metastasis, and cellular signalling events during tumour growth and progression.TMPRSS4 is a novel TTSPs that is highly expressed on the cell surface in pancreatic, thyroid, liver,lung,colon, and other cancer tissues,but its oncogenic significance and molecular mechanisms are unknown.Although our studies using immunohistochemistry have described the high expression of TMPRSS4 in breast cancer specimens compared with the normal tissues, its molecular mechanisms and biological function in breast cancer development are still unclear. In the present work, the expression and biological roles of TMPRSS4 will be studied in the three principal aspects,breast cell lines, animal model and human breast cancer tissues.TMPRSS4 may therefore hold promise as a marker for both prognosis and therapy stratification, and as a therapeutic target in its own right. The cellular signal pathway in EMT merits further investigation,with TMPRSS4 possibly playing a pivotal role in breast cancer development.

Ⅱ型跨膜丝氨酸蛋白酶(Type II transmembrane serine proteases, TTSPs)是一大类位于细胞膜上的蛋白水解酶,TTSPs在上皮-间质转化、恶性肿瘤侵袭转移和肿瘤信号转导中起着重要作用。跨膜丝氨酸蛋白酶4(TMPRSS4)是TTSPs家族中的一员,近年来研究发现TMPRSS4广泛表达于上皮来源的肿瘤细胞中，包括胰腺癌，甲状腺癌、肝癌、肺癌和结直肠癌等。TMPRSS4可能在肿瘤的转移和侵袭过程中起到重要作用，但TMPRSS4对乳腺癌细胞侵袭转移能力的影响尚无相关报道。本课题从人乳腺癌细胞株，裸鼠移植瘤模型和人乳腺癌组织三方面对TMPRSS4与乳腺癌生物学行为的相关性及其作用的分子机制进行研究，从而丰富并加深我们对乳腺癌发展过程的分子病理机制的认识，为乳腺癌的预后判断提供新的依据，为寻找和筛选新的药物关键靶点提供理论依据。

Ⅱ型跨膜丝氨酸蛋白酶(Type II transmembrane serine protease, TTSPs)是一大类位于细胞膜上的蛋白水解酶,在上皮-间质转化、恶性肿瘤侵袭转移、肿瘤信号传递中起着重要作用。跨膜丝氨酸蛋白酶4(TMPRSS4)是TTSPs家族中的一员,近年来研究发现TMPRSS4广泛表达于上皮来源的肿瘤细胞中，包括胰腺癌，甲状腺癌、肝癌、肺癌和结直肠癌等，TMPRSS4可能在肿瘤的转移和侵袭过程中起到重要作用，但TMPRSS4对乳腺癌细胞侵袭转移能力的影响尚无相关报道。本课题从人乳腺癌细胞株，裸鼠移植瘤模型和人乳腺癌组织三方面对TMPRSS4表达与乳腺癌生物学行为的相关关系及其作用的分子机制进行研究。结果显示TMPRSS4在乳腺癌组织中的表达显著高于正常组织。通过慢病毒RNAi干扰技术下调TMPRSS4表达，结果显示下调TMPRSS4表达显著抑制乳腺癌细胞的转移和侵袭，并且影响上皮间质转化过程。通过裸鼠移植瘤模型证明下调TMPRSS4表达可抑制乳腺癌发生过程。综上所述，TMPRSS4作为癌基因参与乳腺癌发生发展过程。通过对TMPRSS4的研究加深我们对乳腺癌发展过程的分子病理机制的认识，为乳腺癌的预后判断提供新的依据，为寻找和筛选新的药物关键靶点提供理论依据。