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The small GTPase RhoA has greater expression in small cell lung carcinoma than in non-small cell lung carcinoma and contributes to their unique morphologies.
- Source :
-
International journal of oncology [Int J Oncol] 2003 Mar; Vol. 22 (3), pp. 671-81. - Publication Year :
- 2003
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Abstract
- The two major forms of lung carcinoma, small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), are clinically distinct, and are also differentiated by morphology and behavior in culture. SCLC cells have a greater metastatic potential than NSCLC cells in vivo, and exhibit a unique spherical morphology in culture due to their inability to adhere and spread on the substratum. Because the small GTPase RhoA affects metastatic properties and regulates cell morphology, we examined whether differences in RhoA expression and activity contribute to the distinct SCLC and NSCLC phenotypes. We found that the expression and GTPgammaS-dependent activation of RhoA are generally greater in SCLC cell lines (SCC-9, NCI-H69, NCI-H146, and NCI-H345) than in NSCLC cell lines (NCI-H23, NCI-H157, NCI-H520, and NCI-H522). The effects of inhibiting Rho-mediated signaling in these cells were investigated by transfecting the cells with cDNA coding for C3 exoenzyme, which ADP-ribosylates and inactivates Rho. Expression of C3 exoenzyme in SCLC cells induces cell-cell compaction, and causes NCI-H345 cells to adhere and spread on collagen IV. In contrast, expression of C3 exoenzyme in NSCLC cells does not induce detectable compaction, but induces cell spreading of NCI-H23 and NCI-H157 cells. Cell proliferation is diminished by Rho inactivation in the majority of the NSCLC cell lines, but not the SCLC cell lines. Expression of p21Cip1/WAF1 is also diminished by Rho inactivation in two of the SCLC cell lines, but is not significantly altered in the NSCLC lines. These results indicate that Rho-mediated signaling may regulate different events in SCLC and NSCLC cells, including adhesion of SCLC cells and proliferation of NSCLC cells.
- Subjects :
- ADP Ribose Transferases genetics
ADP Ribose Transferases metabolism
Adenocarcinoma enzymology
Adenocarcinoma genetics
Adenocarcinoma pathology
Adenosine Diphosphate Ribose metabolism
Botulinum Toxins genetics
Botulinum Toxins metabolism
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Carcinoma, Small Cell genetics
Carcinoma, Small Cell pathology
Carcinoma, Squamous Cell enzymology
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell pathology
Cell Adhesion
Cell Division drug effects
Cell Size
Cyclin-Dependent Kinase Inhibitor p21
Cyclins biosynthesis
Cyclins genetics
DNA, Complementary genetics
Gene Expression Regulation, Neoplastic
Guanosine 5'-O-(3-Thiotriphosphate) pharmacology
Humans
Lung Neoplasms genetics
Lung Neoplasms pathology
Neoplasm Metastasis
Neoplasm Proteins antagonists & inhibitors
Neoplasm Proteins biosynthesis
Neoplasm Proteins genetics
Signal Transduction drug effects
rhoA GTP-Binding Protein antagonists & inhibitors
rhoA GTP-Binding Protein biosynthesis
rhoA GTP-Binding Protein genetics
Carcinoma, Non-Small-Cell Lung enzymology
Carcinoma, Small Cell enzymology
Lung Neoplasms enzymology
Neoplasm Proteins physiology
rhoA GTP-Binding Protein physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1019-6439
- Volume :
- 22
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 12579323