de.mpg.escidoc.pubman.appbase.FacesBean
English
 
Help Guide Disclaimer Contact us Login
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Induction of the Cdk inhibitor p21 by LY83583 inhibits tumor cell proliferation in a p53-independent manner

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons78329

Lodygin,  D.
Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78388

Menssen,  A.
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78098

Hermeking,  H.
Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)
There are no public fulltexts available
Supplementary Material (public)
There is no public supplementary material available
Citation

Lodygin, D., Menssen, A., & Hermeking, H. (2002). Induction of the Cdk inhibitor p21 by LY83583 inhibits tumor cell proliferation in a p53-independent manner. Journal of Clinical Investigation, 110(11), 1717-1727.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-6DCA-1
Abstract
Using microarray analysis, we have detected downregulation of several components of the cGMP signaling pathway during replicative senescence of primary human diploid fibroblasts (HDFs). Therefore, the effect of pharmacological inhibition of cGMP synthesis was analyzed in HDFs. Treatment with 6-anilino- 5,8-quinolinequinone (LY83583, referred to as LY hereafter), a previously described inhibitor of guanylate cyclase, induced cellular senescence. Microarray analysis revealed that LY treatment induced the Cdk inhibitor p21(WAF1/SDI/CIP1). In colorectal cancer cells, transcription of p21 was induced by LY in a p53-independent manner. Furthermore, p21, but not p53, was required for inhibition of proliferation by LY. The lack of p53 involvement suggests that LY does not induce DNA damage. Growth inhibition was also observed in malignant melanoma and breast cancer cell lines. Functional inactivation of the retinoblastoma tumor-suppressor protein, an effector of p21- mediated cell-cycle inhibition, converted LY-induced growth arrest to apoptosis. These results suggest that LY, or derivatives, may be useful therapeutic agents for the treatment of tumors.