HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Forti, F. L Articles by Armelin, H. A Search for Related Content PubMed PubMed Citation Articles by Forti, F. L Articles by Armelin, H. A

Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, Brazil

(Correspondence should be addressed to H A Armelin, Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 748-Bl 09 Inf., Sl 926, Cidade Universitaria, CEP 05508-900, CP 26077, Sao Paulo-SP, Brazil; Email: haarmeli{at}iq.usp.br)

Arginine vasopressin (AVP), a vasoactive peptide hormone that binds to three G-protein coupled receptors (V₁R, V₂R, and V₃R), has long been known to activate V₁R and elicit mitogenesis in several cell types, including adrenal glomerulosa cells. However, in the mouse Y1 adrenocortical malignant cell line, AVP triggers not only a canonical mitogenic response but also novel RhoA-GTP-dependent mechanisms which downregulate cyclin D1, irreversibly inhibiting K-ras oncogene-driven proliferation. In Y1 cells, AVP blocks cyclin D1 expression, induces senescence-associated β-galactosidase (SAβ-Gal) and inhibits proliferation. However, ectopic expression of cyclin D1 renders Y1 cells resistant to both SAβ-Gal induction and proliferation inhibition by AVP. In addition, ectopic expression of the dominant negative RhoAN19 mutant blocks RhoA activation, yielding Y1 cell sub-lines which are no longer susceptible to cyclin D1 downregulation, SAβ-Gal induction, or proliferation inhibition by AVP. Furthermore, inhibiting RhoA with C3 exoenzyme protects Y1 cells from AVP proliferation inhibition and SAβ-Gal induction. On the other hand, AVP treatment does not activate caspases 3 and 7, and the caspase inhibitor Ac-DEVD-CMK does not protect Y1 cells from proliferation inhibition by AVP, implying that AVP does not trigger apoptosis. These results underline a pivotal survival activity of cyclin D1 that protects K-ras oncogene-dependent malignant cells from senescence.

This article has been cited by other articles:

				E. T. Costa, F. L. Forti, T. G.F. Matos, A. Dermargos, F. Nakano, J. Salotti, K. M. Rocha, P. F. Asprino, C. K. Yoshihara, M. M. Koga, et al. Fibroblast Growth Factor 2 Restrains Ras-Driven Proliferation of Malignant Cells by Triggering RhoA-Mediated Senescence Cancer Res., August 1, 2008; 68(15): 6215 - 6223. [Abstract] [Full Text] [PDF]