Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells.

Authors
Yuan-BZ; Jefferson-AM; Millecchia-L; Popescu-NC; Reynolds-SH
Source
Exp Cell Res 2007 Nov; 313(18):3868-3880
NIOSHTIC No.
20032800
Abstract
We have previously shown that reactivation of DLC1, a RhoGAP containing tumor suppressor gene, inhibits tumorigenicity of human non-small cell lung carcinoma cells (NSCLC). After transfection of NSCLC cells with wild type (WT) DLC1, changes in cell morphology were observed. To determine whether such changes have functional implications, we generated several DLC1 mutants and examined their effects on cell morphology, proliferation, migration and apoptosis in a DLC1 deficient NSCLC cell line. We show that WT DLC1 caused actin cytoskeleton-based morphological alterations manifested as cytoplasmic extensions and membrane blebbings in most cells. Subsequently, a fraction of cells exhibiting DLC1 protein nuclear translocation (PNT) underwent caspase 3-dependent apoptosis. We also show that the RhoGAP domain is essential for the occurrence of morphological alterations, PNT and apoptosis, and the inhibition of cell migration. DLC1 PNT is dependent on a bipartite nuclear localizing sequence and most likely is regulated by a serine-rich domain at N-terminal part of the DLC1 protein. Also, we found that DLC1 functions in the cytoplasm as an inhibitor of tumor cell proliferation and migration, but in the nucleus as an inducer of apoptosis. Our analyses provide evidence for a possible link between morphological alterations, PNT and proapoptotic and anti-oncogenic activities of DLC1 in lung cancer.
Keywords
Respiratory-system-disorders; Respiratory-irritants; Cancer; Cell-damage; Cell-metabolism; Cell-morphology; Cellular-function
Contact
Bao-Zhu Yuan, Laboratory of Molecular Genetics, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, CDC, Morgantown, WV 26505
CODEN
ECREAL
Publication Date
20071101
Document Type
Journal Article
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
18
ISSN
0014-4827
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Experimental Cell Research
State
WV; MD
TOP