Loss of cellular adhesion to matrix induces p53-independent expression of PTEN tumor suppressor

BMC Molecular Biology

Axel H Schönthal²  Xinwei Li¹  Martina Blumenthal¹  Ray-Chang Wu³ 

[1] Department of Molecular Microbiology and Immunology, Keck School of Medicine;K. Norris Jr. Comprehensive Cancer Center, University of Southern California, 2011 Zonal Ave, HMR-405, Los Angeles, CA 90089, USA;Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA

关键词: Adhesion;    p53;    Anchorage-dependence;    PTEN;    Tumor Suppressor;   

Others  :  1142328
DOI  :  10.1186/1471-2199-3-11

 received in 2002-04-18, accepted in 2002-07-12,  发布年份 2002

【 摘 要 】

Background

The tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, exogenous PTEN was able to suppress their ability to grow anchorage-independently, and thus reverted one of the typical characteristics of tumor cells. As these findings indicated that PTEN might be involved in the regulation of anchorage-dependent cell growth, we analyzed this aspect of PTEN function in non-tumor cells with an anchorage-dependent phenotype.

Results

We found that in response to the disruption of cell-matrix interactions, expression of endogenous PTEN was transcriptionally activated, and elevated levels of PTEN protein and activity were present in the cells. These events correlated with decreased phosphorylation of focal adhesion kinase, and occurred even in the absence of p53, a tumor suppressor protein and recently established stimulator of PTEN transcription.

Conclusions

In view of PTEN's potent growth-inhibitory capacity, we conclude that its induction after cell-matrix disruptions contributes to the maintenance of the anchorage-dependent phenotype of normal cells.

【 授权许可】

   
2002 Wu et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

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