乳腺癌与细胞外信号调节激酶/丝裂原活化蛋白激酶关系的研究进展

Research Progress on Correlation between Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase and Breast Cancer

在信号网络中丝裂原活化蛋白激酶(MAPK)信号传递途径起着极为重要的作用,MAPK异常活化导致细胞分化、凋亡功能的丧失,引起细胞恶性转化,异常增殖、肿瘤发生、侵袭能力增强,最终导致肿瘤转移。细胞外信号调节激酶(ERK)是MAPK家族极其重要的一员,它的信号传递途径是涉及调节细胞生长、发育及分裂的信号网络的核心,其基本的信号传递步骤已明确,遵循MAPKs的三级酶促级联反应,即上游激活蛋白→MAPK激酶激酶(MAPKKK)→MAPK激酶(MAPKK)→MAPK。在ERKs的传递途径中,Ras作为上游激活蛋白,Raf作为MAPKKK,MAPK/ERK激酶(MEK)作为MAPKK,ERK即MAPK,即Ras-Raf-MEK-ERK途径,它是表皮生长因子受体(EGFR)信号传导通路最主要的通路之一,主要调节细胞增殖和生长。在恶性肿瘤尤其是乳腺癌的发生、发展、浸润和转移方面都起着重要的作用。

In the signaling network, mitogen - activated protein kinase （MAPK） signaling pathway plays an extremely important role. The abnormal activation of MAPK will lead to the loss of cell differentiation and apoptosis function, resulting in malignant transformation, abnormal proliferation, tumorigenesis, enhancement of the invasive ability and ultimately tumor metas- tasis. Extracellular signal -regulated kinase （ERK） is an important member in MAPK family. Its signaling pathway is involved inthe core of the signaling networks that regulate cell growth, development and division. The basic steps of the signaling have been clear to us. It follows the reaction of the three enzymatic cascades of MAPKs, namely： the upstream activating protein → MAPK kinase kinase （MAPKKK） → MAPK kinase （MAPKK） → the MAPK. In the ERKs pathway, Ras is an upstream activating pro-tein ; Raf is MAPKKK, MAPK / ERK kinase （MEK） as MAPKK, ERK or MAPK, which is Ras - Raf - MEK - ERK path- way. It is one of the most important pathways of the epidermal growth factor receptor （EGFR） signaling pathway and the major reg- ulator of cell proliferation and growth. MAPK plays an important role especially in the occurrence of breast cancer development, invasion and metastasis in malignant tumors.