Document Detail


Cell cycle deregulation and xeroderma pigmentosum group C cell transformation.
MedLine Citation:
PMID:  12485438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously described a genetically unstable human fibroblast cell strain (GM2995), isolated from normal appearing skin of a xeroderma pigmentosum group C patient that repeatedly underwent changes characteristic of the transformed phenotype upon serial cultivation in vitro. In order to gain information concerning genetic changes associated with the transformation of this xeroderma pigmentosum group C cell strain, we examined the expression/function of several cell cycle regulators during its serial cultivation. A mutation in exon 8 of the P53 gene was associated with loss of function of the p53 protein and appeared at about the same time that transformation occurred. Abnormal P53 function was confirmed by the lack of upregulation of p53 as well as activation of its downstream effectors p21Waf1 and HDM2 in high passage cells exposed to either gamma irradiation or ultraviolet C irradiation. Consistent with deregulation in cell cycle control, persistent hyper-phosphorylation of the retinoblastoma protein and lack of a decrease in p34cdc2 were observed in irradiated cells. Furthermore, retinoblastoma protein remained hyperphosphorylated in control high passage confluent cultures that were serum starved for 72 h. Compared with low passage cells, the expression levels of the cyclin-dependent kinase inhibitor p27Kip1 were significantly reduced and the pattern of expression of the von Hippel-Lindau protein was aberrant. These data indicate that the process of cellular transformation of this xeroderma pigmentosum group C cell strain involves the progressive acquisition of mutations and abnormalities in the expression/function of several cell cycle regulators.
Authors:
Edouard I Azzam; Hatsumi Nagasawa; Yongjia Yu; Chuan-Yuan Li; John B Little
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  119     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-17     Completed Date:  2003-01-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1350-4     Citation Subset:  IM    
Affiliation:
Laboratory of Radiobiology, Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
CDC2 Protein Kinase / genetics
Cell Communication
Cell Cycle Proteins / genetics
Cell Transformation, Neoplastic*
Cells, Cultured
Child
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Cyclins / genetics
Fibroblasts / cytology*
Humans
Infant
Ligases / genetics
Male
Mutation
Nuclear Proteins*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-mdm2
Retinoblastoma Protein / genetics
Skin / cytology*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Proteins / genetics
Ubiquitin-Protein Ligases*
Von Hippel-Lindau Tumor Suppressor Protein
Xeroderma Pigmentosum / pathology,  physiopathology*
Grant Support
ID/Acronym/Agency:
CA47542/CA/NCI NIH HHS; ES-00002/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.22/CDC2 Protein Kinase; EC 6.-/Ligases; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/VHL protein, human; EC 6.3.2.19/Von Hippel-Lindau Tumor Suppressor Protein

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