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学科主题: 临床医学
题名:
Smad4 and ERK2 stimulated by transforming growth factor betal in rhabdomyosarcoma
作者: Guo Hua1; Zhang Hong-ying1; Wang Shou-li1; Ye Lu1; Yang Guang-hua1; Bu Hong1
关键词: transforming growth factor beta1 ; mitogen-activated prtein kinase ; Smad4 ; rhabdomyosarcoma
刊名: CHINESE MEDICAL JOURNAL
发表日期: 2007-03-20
卷: 120, 期:6, 页:515-521
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, General & Internal
研究领域[WOS]: General & Internal Medicine
关键词[WOS]: ACTIVATED PROTEIN-KINASE ; TGF-BETA ; SIGNALING PATHWAYS ; MAP KINASE ; CROSS-TALK ; CELLS ; JNK ; DIFFERENTIATION ; REQUIRES
英文摘要:

Background Transforming growth factor beta (TGF-beta) plays an essential role in the regulation of normal physiologic processes of cells. TGF-beta has been shown to regulate several mitogen-activated protein kinases (MAPK) pathways in several epithelial cells. However, the effects of TGF-beta on soft tissue sarcoma are seldom reported. Our previous studies suggested that there should be some other signal transduction pathways besides Smads, which are important to regulate the growth of human embryonal rhabdomyosarcoma (RMS) cells. In the present study, we examined the expression and functional relations of extracellular signal-regulated kinase 2 (ERK2) and Smad4 in human RMS tissue and a RMS cell line, RD.

Methods RD cells and normal human primary skeletal myoblasts (Mb) were treated with TGF-betal to establish the expression profile of ERK2 at the mRNA and protein levels detected by RT-PCR and immunofluorescence. Immunohistochemistry was used to detect the expression of ERK2 and Smad4 in 50 tissue specimens of human RMS and 23 specimens of normal skeletal muscles. Follow-up of specimens was performed 6 months to 70 months later.

Results RD cells and human RMS tissues showed the higher expression of ERK2 and Smad4 than the normal control, either the protein level or the mRNA level. And, exogenous TGF-betal stimulation can lead to higher expression of ERK2 and its nuclear translocation, so TGF-beta1 can also activated MAPK (ERK2) pathway, resulting in a sustained activation of ERK2 for at least 2 hours. Immunohistochemistry analysis, however, showed that there was no correlation between ERK2 and Smad4 protein. The overexpression of ERK2 and Smad4 had no indicative effects on histological subtypes, histological grading, gender, age, and prognosis.

Conclusions In RMS, signaling of TGF-beta1 from cell surface to nucleus can also be directed through the MAPK (ERK2) pathway besides the TGF-beta1/Smads pathway. The activation of ERK2 by TGF-beta1 may be Smad4 independent. Moreover, there may be some other tanglesome relationships between the TGF-beta1/Smads pathway and the MAPK pathway which takes part in the development, invasion and metastasis of tumor cells.

语种: 英语
WOS记录号: WOS:000245453400015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52089
Appears in Collections:北京大学第一临床医学院_病理科_期刊论文

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作者单位: 1.Sichuan Univ, W China Hosp, Dept Pathol, Chengdu 610041, Peoples R China
2.Peking Univ, Hosp 1, Dept Pathol, Beijing 100034, Peoples R China
3.Peking Univ, W China Hosp, Dept Pathol, Beijing 100034, Peoples R China

Recommended Citation:
Guo Hua,Zhang Hong-ying,Wang Shou-li,et al. Smad4 and ERK2 stimulated by transforming growth factor betal in rhabdomyosarcoma[J]. CHINESE MEDICAL JOURNAL,2007,120(6):515-521.
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