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Cell cycle deregulation and xeroderma pigmentosum group C cell transformation.

Publication ,  Journal Article
Azzam, EI; Nagasawa, H; Yu, Y; Li, C-Y; Little, JB
Published in: J Invest Dermatol
December 2002

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.

Duke Scholars

Published In

J Invest Dermatol

DOI

ISSN

0022-202X

Publication Date

December 2002

Volume

119

Issue

6

Start / End Page

1350 / 1354

Location

United States

Related Subject Headings

  • Xeroderma Pigmentosum
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ubiquitin-Protein Ligases
  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Skin
  • Retinoblastoma Protein
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins
  • Nuclear Proteins
 

Citation

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MLA
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Azzam, E. I., Nagasawa, H., Yu, Y., Li, C.-Y., & Little, J. B. (2002). Cell cycle deregulation and xeroderma pigmentosum group C cell transformation. J Invest Dermatol, 119(6), 1350–1354. https://doi.org/10.1046/j.1523-1747.2002.19628.x
Azzam, Edouard I., Hatsumi Nagasawa, Yongjia Yu, Chuan-Yuan Li, and John B. Little. “Cell cycle deregulation and xeroderma pigmentosum group C cell transformation.J Invest Dermatol 119, no. 6 (December 2002): 1350–54. https://doi.org/10.1046/j.1523-1747.2002.19628.x.
Azzam EI, Nagasawa H, Yu Y, Li C-Y, Little JB. Cell cycle deregulation and xeroderma pigmentosum group C cell transformation. J Invest Dermatol. 2002 Dec;119(6):1350–4.
Azzam, Edouard I., et al. “Cell cycle deregulation and xeroderma pigmentosum group C cell transformation.J Invest Dermatol, vol. 119, no. 6, Dec. 2002, pp. 1350–54. Pubmed, doi:10.1046/j.1523-1747.2002.19628.x.
Azzam EI, Nagasawa H, Yu Y, Li C-Y, Little JB. Cell cycle deregulation and xeroderma pigmentosum group C cell transformation. J Invest Dermatol. 2002 Dec;119(6):1350–1354.
Journal cover image

Published In

J Invest Dermatol

DOI

ISSN

0022-202X

Publication Date

December 2002

Volume

119

Issue

6

Start / End Page

1350 / 1354

Location

United States

Related Subject Headings

  • Xeroderma Pigmentosum
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ubiquitin-Protein Ligases
  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Skin
  • Retinoblastoma Protein
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins
  • Nuclear Proteins