Cell cycle deregulation and xeroderma pigmentosum group C cell transformation

Edouard I. Azzam, Hatsumi Nagasawa, Yongjia Yu, Chuan Yuan Li, John B. Little

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 c irradiation or ultraviolet C irradiation. Consistent with deregulation in cell cycle control, persistent hyperphosphorylation 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.

Original languageEnglish (US)
Pages (from-to)1350-1354
Number of pages5
JournalJournal of Investigative Dermatology
Volume119
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Xeroderma Pigmentosum
Deregulation
Cell Cycle
Cells
Retinoblastoma Protein
Irradiation
Cyclin-Dependent Kinases
Fibroblasts
Mutation
p53 Genes
Exons
Cell Cycle Checkpoints
Skin
Proteins
Genes
Chemical activation
Up-Regulation
Phenotype
Serum

Keywords

  • Cell cycle regulation
  • Genomic instability
  • p27
  • p53
  • Xeroderma pigmentosum

ASJC Scopus subject areas

  • Dermatology

Cite this

Cell cycle deregulation and xeroderma pigmentosum group C cell transformation. / Azzam, Edouard I.; Nagasawa, Hatsumi; Yu, Yongjia; Li, Chuan Yuan; Little, John B.

In: Journal of Investigative Dermatology, Vol. 119, No. 6, 2002, p. 1350-1354.

Research output: Contribution to journalArticle

Azzam, Edouard I. ; Nagasawa, Hatsumi ; Yu, Yongjia ; Li, Chuan Yuan ; Little, John B. / Cell cycle deregulation and xeroderma pigmentosum group C cell transformation. In: Journal of Investigative Dermatology. 2002 ; Vol. 119, No. 6. pp. 1350-1354.
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