NDLI: The RASSF1A Isoform of RASSF1 Promotes Microtubule Stability and Suppresses Tumorigenesis

Content Provider	PubMed Central
Author	Weyden, L. Van Der Tachibana, K. K. Gonzalez, M. A. Adams, D. J. Ng, B. L. Petty, R. Venkitaraman, A. R. Arends, M. J. Bradley, A.
Copyright Year	2005
Abstract	The RASSF1A isoform of RASSF1 is frequently inactivated by epigenetic alterations in human cancers, but it remains unclear if and how it acts as a tumor suppressor. RASSF1A overexpression reduces in vitro colony formation and the tumorigenicity of cancer cell lines in vivo. Conversely, RASSF1A knockdown causes multiple mitotic defects that may promote genomic instability. Here, we have used a genetic approach to address the function of RASSF1A as a tumor suppressor in vivo by targeted deletion of Rassf1A in the mouse. Rassf1A null mice were viable and fertile and displayed no pathological abnormalities. Rassf1A null embryonic fibroblasts displayed an increased sensitivity to microtubule depolymerizing agents. No overtly altered cell cycle parameters or aberrations in centrosome number were detected in Rassf1A null fibroblasts. Rassf1A null fibroblasts did not show increased sensitivity to microtubule poisons or DNA-damaging agents and showed no evidence of gross genomic instability, suggesting that cellular responses to genotoxins were unaffected. Rassf1A null mice showed an increased incidence of spontaneous tumorigenesis and decreased survival rate compared with wild-type mice. Irradiated Rassf1A null mice also showed increased tumor susceptibility, particularly to tumors associated with the gastrointestinal tract, compared with wild-type mice. Thus, our results demonstrate that Rassf1A acts as a tumor suppressor gene.
Related Links	http://dx.doi.org/10.1128/mcb.25.18.8356-8367.2005
Ending Page	8367
Page Count	12
Starting Page	8356
File Format	PDF
ISSN	02707306
e-ISSN	10985549
Journal	Molecular and Cellular Biology
Issue Number	18
Volume Number	25
Language	English
Publisher	American Society for Microbiology
Publisher Date	2005-09-15
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Cell Biology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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