In:
Cancer Science, Wiley, Vol. 103, No. 9 ( 2012-09), p. 1640-1650
Kurzfassung:
Increasing evidence suggests that PRMT 5, a protein arginine methyltransferase, is involved in tumorigenesis. However, no systematic research has demonstrated the cell‐transforming activity of PRMT 5. We investigated the involvement of PRMT 5 in tumor formation. First, we showed that PRMT 5 was associated with many human cancers, through statistical analysis of microarray data in the NCBI GEO database. Overexpression of ectopic PRMT 5 per se or its specific sh RNA enhanced or reduced cell growth under conditions of normal or low concentrations of serum, low cell density, and poor cell attachment. A stable clone that expressed exogenous PRMT 5 formed tumors in nude mice, which demonstrated that PRMT 5 is a potential oncoprotein. PRMT 5 accelerated cell cycle progression through G 1 phase and modulated regulators of G 1; for example, it upregulated cyclin‐dependent kinase ( CDK ) 4, CDK 6, and cyclins D 1, D 2 and E 1, and inactivated retinoblastoma protein ( R b). Moreover, PRMT 5 activated phosphoinositide 3‐kinase ( PI 3K)/ AKT and suppressed c‐ J un N ‐terminal kinase ( JNK )/c‐ J un signaling cascades. However, only inhibition of PI 3 K activity, and not overexpression of JNK , blocked PRMT 5‐induced cell proliferation. Further analysis of PRMT 5 expression in 64 samples of human lung cancer tissues by microarray and western blot analysis revealed a tight association of PRMT 5 with lung cancer. Knockdown of PRMT 5 retarded cell growth of lung cancer cell lines A 549 and H 1299. In conclusion, to the best of our knowledge, we have characterized the cell‐transforming activity of PRMT 5 and delineated its underlying mechanisms for the first time.
Materialart:
Online-Ressource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2012.103.issue-9
DOI:
10.1111/j.1349-7006.2012.02367.x
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2012
ZDB Id:
2115647-5
ZDB Id:
2111204-6
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