Skip to main content
SpringerLink
Log in

The role of XPD in cell apoptosis and viability and its relationship with p53 and cdk2 in hepatoma cells

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

We investigated the role of XPD in cell apoptosis of hepatoma and its relationship with p53 during the regulation of hepatoma bio-behavior. RT–PCR and Western blot were used to detect the expression levels of XPD, p53, c-myc, and cdk2. The cell apoptosis and cell cycle were analyzed with flow cytometry. Compared with the control cells, XPD-transfected cells displayed a lower viability and higher apoptosis rate. A decreased expression of p53 gene was detected in XPD-transfected cells. In contrast, both c-myc and cdk2 showed increased expressions of mRNAs and proteins in the transfected cells. Our results indicate that XPD may play an important role in cell apoptosis of hepatoma by inducing an over-expression of p53, but suppressing expressions of c-myc and cdk2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Emmert S, Leibeling D, Rünger TM. Syndromes with genetic instability: model diseases for (skin) cancerogenesis. J Dtsch Dermatol Ges. 2006;4:721–31.

    Article  PubMed  Google Scholar 

  2. Zhang J, Powell SN. The role of the BRCA1 tumor suppressor in DNA double-strand break repair. Mol Cancer Res. 2005;3:531–9.

    Article  PubMed  CAS  Google Scholar 

  3. Nakajima S, Lan L, Kanno S, Takao M, Yamamoto K, Eker AP, Yasui A. UV light-induced DNA damage and tolerance for the survival of nucleotide excision repair-deficient human cells. J Biol Chem. 2004;279:46674–7.

    Article  PubMed  CAS  Google Scholar 

  4. Lehmann AR. DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie. 2003;85:1101–11.

    Article  PubMed  CAS  Google Scholar 

  5. Sung P, Bailly V, Weber C, Thompson LH, Prakash L, Prakash S. Human xeroderma pigmentosum group D gene encodes a DNA helicase. Nature. 1993;365:852–5.

    Article  PubMed  CAS  Google Scholar 

  6. Coin F, Marinoni J-C, Rodolfo C, Fribourg S, Pedrini AM, Egly J-M. Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH. Nature Genet. 1998;20:184–8.

    Article  PubMed  CAS  Google Scholar 

  7. Lainé JP, Mocquet V, Bonfanti M, Braun C, Egly JM, Brousset P. Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription. DNA Repair (Amst). 2007;6:1264–70.

    Article  Google Scholar 

  8. Robles AI, Harris CC. p53-mediated apoptosis and genomic instability diseases. Acta Oncol. 2001;40:696–701.

    Article  PubMed  CAS  Google Scholar 

  9. Askin DF, Diehl-Jones WL. The neonatal liver: part III: pathophysiology of liver dysfunction. Neonatal Netw. 2003;22:5–15.

    PubMed  Google Scholar 

  10. Becker SA, Lee TH, Butel JS, Slagle BL. Hepatitis B virus X protein interferes with cellular DNA repair. J Virol. 1998;72:266–72.

    PubMed  CAS  Google Scholar 

  11. Jaitovich-Groisman I, Benlimame N, Slagle BL, Perez MH, Alpert L, Song DJ, Fotouhi-Ardakani N, Galipeau J, Alaoui-Jamali MA. Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue. J Biol Chem. 2001;276:14124–32.

    PubMed  CAS  Google Scholar 

  12. Uhring M, Poterszman A. DNA helicases and human diseases. Med Sci (Paris). 2006;22:1087–94.

    Article  Google Scholar 

  13. Capovilla A, Arbuthnot P. Nucleotide excision repair by extracts of human fetal hepatocytes. FEBS Lett. 2002;518:144–8.

    Article  PubMed  CAS  Google Scholar 

  14. Robles AI, Wang XW, Harris CC. Drug-induced apoptosis is delayed and reduced in XPD lymphoblastoid cell lines: possible role of TFIIH in p53-mediated apoptotic cell death. Oncogene. 1999;18:4681–8.

    Article  PubMed  CAS  Google Scholar 

  15. Jia L, Wang XW, Harris CC. Hepatitis B virus X protein inhibits nucleotide excision repair. Int J Cancer. 1999;80:875–9.

    Article  PubMed  CAS  Google Scholar 

  16. Giebler HA, Lemasson I, Nyborg JK. p53 recruitment of CREB binding protein mediated through phosphorylated CREB: a novel pathway of tumor suppressor regulation. Mol Cell Biol. 2000;20:4849–58.

    Article  PubMed  CAS  Google Scholar 

  17. Smith ML, Ford JM, Hollander MC, Bortnick RA, Amundson SA, Seo YR, Deng CX, Hanawalt PC, Fornace AJ Jr. p53-mediated DNA repair responses to UV radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes. Mol Cell Biol. 2000;20:3705–14.

    Article  PubMed  CAS  Google Scholar 

  18. Léveillard T, Andera L, Bissonnette N, Schaeffer L, Bracco L, Egly JM, Wasylyk B. Functional interactions between p53 and the TFIIH complex are affected by tumour-associated mutations. EMBO J. 1996;15:1615–24.

    PubMed  Google Scholar 

  19. Wang XW, Vermeulen W, Coursen JD, Gibson M, Lupold SE, Forrester K, Xu G, Elmore L, Yeh H, Hoeijmakers JH, Harris CC. The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. Genes Dev. 1996;10:1219–32.

    Article  PubMed  CAS  Google Scholar 

  20. Cadoret A, Ovejero C, Saadi-Kheddouci S, Souil E, Fabre M, Romagnolo B, Kahn A, Perret C. Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin. Cancer Res. 2001;61:3245–9.

    PubMed  CAS  Google Scholar 

  21. Calvisi DF, Ladu S, Hironaka K, Factor VM, Thorgeirsson SS. Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic mouse model of liver cancer. J Hepatol. 2004;41:815–22.

    Article  PubMed  CAS  Google Scholar 

  22. Hamajima N, Saito T, Matsuo K, Suzuki T, Nakamura T, Matsuura A, Okuma K, Tajima K. Genotype frequencies of 50 polymorphisms for 241 Japanese non-cancer patients. J Epidemiol. 2002;12:229–36.

    Article  PubMed  Google Scholar 

  23. Liu J, Akoulitchev S, Weber A, Ge H, Chuikov S, Libutti D, Wang XW, Conaway JW, Harris CC, Conaway RC, Reinberg D, Levens D. Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum. Cell. 2001;104:353–63.

    Article  PubMed  CAS  Google Scholar 

  24. Liu J, He L, Collins I, Ge H, Libutti D, Li J, Egly JM, Levens D. The FBP interacting repressor targets TFIIH to inhibit activated transcription. Mol Cell. 2000;5:331–41.

    Article  PubMed  CAS  Google Scholar 

  25. Weber A, Liu J, Collins I, Levens D. TFIIH operates through an expanded proximal promoter to fine-tune c-myc expression. Mol Cell Biol. 2005;25:147–61.

    Article  PubMed  CAS  Google Scholar 

  26. Adamczewski JP, Rossignol M, Tassan JP, Nigg EA, Moncollin V, Egly JM. MAT1, cdk7 and cyclin H form a kinase complex which is UV light-sensitive upon association with TFIIH. EMBO J. 1996;15:1877–84.

    PubMed  CAS  Google Scholar 

  27. Lolli G, Johnson LN. Recognition of Cdk2 by Cdk7. Proteins. 2007;67:1048–59.

    Article  PubMed  CAS  Google Scholar 

  28. Chen J, Larochelle S, Li X, Suter B. Xpd/Ercc2 regulates CAK activity and mitotic progression. Nature. 2003;424:228–32.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Junling Yang from Institute of Zoology, Chinese Academy of Sciences for enormous help. This work was supported by National Natural Science Foundation of China, No. 30360037.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Second Affiliated Hospital, Nanchang University, 330006, Nanchang City, Jiangxi, People’s Republic of China

    Hong-yun Wang & Ji-xiang Zhang

  2. Department of Physiology of Medical College, Nanchang University, 330006, Nanchang City, Jiangxi, People’s Republic of China

    Gao-fei Xiong, Hong Xu & Xiang-yang Xiong

  3. Jiangxi Provincial Key Laboratory of Molecular Medicine, 330006, Nanchang City, Jiangxi, People’s Republic of China

    Hong-yun Wang, Gao-fei Xiong, Ji-xiang Zhang, Wu-hua Guo & Jiang-jing Xu

Authors
  1. Hong-yun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gao-fei Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ji-xiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wu-hua Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiang-jing Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiang-yang Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ji-xiang Zhang.

Additional information

The co-first authors, Hong-yun Wang and Gao-fei Xiong, made equal contribution to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Hy., Xiong, Gf., Zhang, Jx. et al. The role of XPD in cell apoptosis and viability and its relationship with p53 and cdk2 in hepatoma cells. Med Oncol 29, 161–167 (2012). https://doi.org/10.1007/s12032-011-9818-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-9818-y

Keywords

Search

Navigation