|The role of Rac1 in maintaining malignant phenotype of mouse skin tumor cells.|
|PMID: 15893875 Owner: NLM Status: MEDLINE|
|We have previously developed an in vitro tumor progression model with mouse skin keratinocytes to study the molecular targets that mediate the tumor cell's progression from a benign to a malignant phenotype. The malignantly transformed cells were found to have elevated MAP kinase signaling and increases in AP-1, NFkappaB and cAMP response element (CRE) transcription factors activities compared to their benign counter-part. In this study, we showed that Rac1, a member of the Rho superfamily of small GTPases, functions as a key signaling molecule that mediates these malignant phenotypes. We used a doxycycline inducible system to express dominant negative Rac1 (N17 Rac1) in the squamous cell carcinomas producing 6M90 cell line. Conditional expression of the N17 Rac1 was able to decrease multiple markers of malignancy including: growth rate, colony formation, migration, invasion and most importantly, in vivo tumor growth. In addition, these phenotypic changes were accompanied by decreases in mitogenic signals, which include ERK1/2, JNK, and PI-3 kinase/Akt activation. Transactivation mediated by AP-1, NFkappaB, and CRE were also attenuated by expression of dominant negative Rac1. These observations led us to conclude that Rac1 signaling is required for the malignant phenotypes of the squamous cell carcinoma cells.|
|Kevin A Kwei; Joanne S Finch; James Ranger-Moore; G Tim Bowden|
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|Type: Journal Article; Research Support, N.I.H., Extramural|
|Title: Cancer letters Volume: 231 ISSN: 0304-3835 ISO Abbreviation: Cancer Lett. Publication Date: 2006 Jan|
|Created Date: 2006-01-09 Completed Date: 2006-03-09 Revised Date: 2014-02-07|
Medline Journal Info:
|Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland|
|Languages: eng Pagination: 326-38 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Anti-Bacterial Agents / pharmacology
Carcinoma, Squamous Cell / metabolism, pathology, prevention & control
Cell Transformation, Neoplastic*
Colony-Forming Units Assay
Cyclic AMP Response Element-Binding Protein / metabolism
Doxycycline / pharmacology
MAP Kinase Kinase 4 / metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
NF-kappa B / genetics, metabolism
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Skin Neoplasms / metabolism*, pathology*, prevention & control
Transcription Factor AP-1 / metabolism
rac1 GTP-Binding Protein / antagonists & inhibitors, genetics, metabolism*
|CA09213/CA/NCI NIH HHS; CA23074/CA/NCI NIH HHS; CA40584/CA/NCI NIH HHS; P30 CA023074/CA/NCI NIH HHS; T32 CA009213/CA/NCI NIH HHS|
|0/Anti-Bacterial Agents; 0/Cyclic AMP Response Element-Binding Protein; 0/NF-kappa B; 0/Transcription Factor AP-1; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 22.214.171.124/Proto-Oncogene Proteins c-akt; EC 126.96.36.199/Mitogen-Activated Protein Kinase 1; EC 188.8.131.52/Mitogen-Activated Protein Kinase 3; EC 184.108.40.206/MAP Kinase Kinase 4; EC 220.127.116.11/rac1 GTP-Binding Protein; N12000U13O/Doxycycline|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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