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学科主题: 基础医学
题名:
Protein kinase C zeta is required for epidermal growth factor-induced chemotaxis of human breast cancer cells
作者: Sun, RH; Gao, P; Chen, L; Ma, DL; Wang, JM; Oppenheim, JJ; Zhang, N
刊名: CANCER RESEARCH
发表日期: 2005-02-15
卷: 65, 期:4, 页:1433-1441
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: CHEMOKINE RECEPTORS ; ACTIN POLYMERIZATION ; LEADING-EDGE ; MOTILITY ; ACTIVATION ; POLARITY ; CDC42 ; MIGRATION ; INTEGRIN ; 3-KINASE
英文摘要:

Chemotaxis plays an important role in cancer cell metastasis. In this study, we showed that epidermal growth factor (EGF) was a more potent chemoattractant than chemokine SDF-1alpha/CXCL12 for human breast cancer cell MDA-MB-231. Different inhibitors were used to evaluate the involvement of 12 protein kinase C (PKC) isotypes in the chemotactic signaling pathway. Chelerythrine chloride, an inhibitor of all PKC isotypes, blocked chemotaxis, whereas inhibitors of classic and novel PKC, such as Go6976, Go6850, or calphostin C, only impaired EGF-induced chemotaxis to a minor extent by not greater than32% inhibition. These data suggested that atypical PKC were involved. The ligand-induced actin polymerization and cell adhesion were also similarly dependent on atypical PKC. Immunofluorescent staining showed an EGF-induced, LY294002- sensitive translocation of PKCzeta from the cytosol to the plasma membrane, indicating that EGF was capable of activating PKCzeta, probably via phosphoinositide 3 kinases. A myristoylated PKCzeta pseudosubstrate blocked the chemotaxis with an IC50 of 20 mumol/L. To expand our investigation, we further showed that in MCF-7 and T47D, two additional human breast cancer cell lines, EGF-activated PKCzeta and the PKCzeta pseudosubstrate, inhibited chemotaxis. Taken together, our data suggest that PKCzeta is an essential component of the EGF-stimulated chemotactic signaling pathway in human breast cancer cells.

语种: 英语
WOS记录号: WOS:000226997800040
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59589
Appears in Collections:基础医学院_生物化学与分子生物学系_期刊论文

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作者单位: 1.Peking Univ, Dept Biol Chem, Beijing 100871, Peoples R China
2.Peking Univ, State Key Lab Mol Dynam & Stable Struct, Coll Chem, Beijing 100871, Peoples R China
3.Peking Univ, Lab Med Immunol, Sch Basic Med Sci, Beijing 100871, Peoples R China
4.NCI, Mol Immunoregulat Lab, Ctr Canc Res, Intramural Res Support Program, Frederick, MD 21701 USA

Recommended Citation:
Sun, RH,Gao, P,Chen, L,et al. Protein kinase C zeta is required for epidermal growth factor-induced chemotaxis of human breast cancer cells[J]. CANCER RESEARCH,2005,65(4):1433-1441.
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