Document Detail

Role of p21 and cyclin E in normal and secalonic acid D-inhibited proliferation of human embryonic palatal mesenchymal cells.
MedLine Citation:
PMID:  20956459     Owner:  NLM     Status:  In-Data-Review    
Secalonic acid D (SAD), a cleft palate-inducing teratogen, has been shown to inhibit proliferation/cell cycle progression in association with alteration in the levels of cell cycle regulators, p21 and cyclin E. These studies were conducted to test the hypotheses that p21 and cyclin E play an important functional role in normal human embryonic palatal mesenchymal (HEPM) cell cycle and that their up- and down-regulation, respectively, by SAD is functionally significant to its cell cycle block. Using small interfering RNA (siRNA) to silence p21gene and transient transfection to overexpress cyclin E in control & SAD-treated HEPM cells, cell proliferation was assessed using a combination of cell numbers, thymidine uptake, CDK2 activity and Ki-67 expression. The results showed that silencing of p21 gene, although increased cell proliferation/numbers and CDK2 activity in normal HEPM cells, failed to counteract SAD-induced anti-proliferative effect despite inducing partial recovery of CDK2 activity. Similar effects were apparent with cyclin E overexpression. It is concluded that p21 and cyclin E are important for normal HEPM cell proliferation. However, SAD-induced deregulation of either protein, singly, may not be sufficient to induce anti-proliferative effect. Involvement of other cell cycle proteins such as cyclin D1 or of multiple proteins in SAD-induced cell cycle block needs to be examined.
Vamsidhara C Dhulipala; Kamala K Maddali; Bimal K Ray; Wade V Welshons; Chada S Reddy
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Publication Detail:
Type:  Journal Article     Date:  2010-10-18
Journal Detail:
Title:  Human & experimental toxicology     Volume:  30     ISSN:  1477-0903     ISO Abbreviation:  Hum Exp Toxicol     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9004560     Medline TA:  Hum Exp Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1222-32     Citation Subset:  IM    
1Department of Safety Assessment, Merck & Co, West Point, PA, USA.
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