期刊
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
卷 135, 期 1, 页码 69-80出版社
SPRINGER
DOI: 10.1007/s00432-008-0437-8
关键词
Tiam1; Rac; Transgenic mice; Mammary tumors; Neu; Myc; MMTV
类别
资金
- Sixth Framework Program of the European Union (BRECOSM)
- Dutch Cancer Society
Background Rho-like small GTPases, including RhoA, Rac1 and Cdc42, are crucial for the regulation of a large variety of biological processes such as the cytoskeletal organization and gene transcription. The activities of Rho GTPases are predominantly controlled by guanine nucleotide exchange factors ( GEFs), which activate GTPases by catalyzing the exchange of bound GDP for GTP. Earlier, we have identified the Tiam1 gene as an invasion-inducing gene that encodes a specific activator (GEF) of the Rac GTPase. We found that Tiam1-mediated Rac signaling functions in various aspects of tumorigenicity including the formation and progression of Ras-induced skin tumors and Wnt-induced intestinal tumors. Here, we further distinguish the oncogenic pathways that depend on Tiam1 signaling in the mammary gland. Material and methods We crossed Tiam1 knockout mice with MMTV-c-myc and MMTV-c-neu transgenic mice, in which the expression of both oncogenes is targeted to the mammary gland leading to mammary tumorigenesis. Results We found Tiam1 important for Neu-induced tumor formation and progression but not for Myc-induced tumors. Tiam1-deficiency delayed Neu-induced tumor initiation and reduced metastasis but had no effect on the growth of the MMTV-c-neu tumors. Conclusion Our data indicate that the Rac activator Tiam1 contributes to tumorigenicity induced by specific oncogenic signaling pathways only.
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