Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines

  • Authors:
    • Lovisa Farnebo
    • Adam Jedlinski
    • Anna Ansell
    • Linda Vainikka
    • Lena K. Thunell
    • Reidar Grénman
    • Ann-Charlotte Johansson
    • Karin Roberg
  • View Affiliations

  • Published online on: October 1, 2009     https://doi.org/10.3892/ijmm_00000264
  • Pages:549-556
0

Abstract

The present study was undertaken to evaluate the possibility of using a panel of proteins and single nucleotide polymorphisms (SNPs) involved in apoptosis, growth control, and DNA repair as predictive markers for cisplatin sensitivity. For this purpose the intrinsic cisplatin sensitivity (ICS) was determined in 39 cell lines derived from squamous cell carcinomas of the head and neck using a colony-forming assay. In these cell lines and in normal oral keratinocytes (NOK), the expression of epidermal growth factor receptor (EGFR), Hsp70, Bax, Bcl-2, Bcl-XL, survivin, and COX-2 was determined. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearson's correlation test showed that EGFR was the only protein that was significantly correlated to the ICS (r=0.388, p=0.015). The combination of EGFR, Hsp70, Bax, and Bcl-2 gave the strongest correlation (r=0.566, p≤0.001), whereas Bax alone had the second highest influence on the ICS. Furthermore, all four SNPs within genes involved in DNA repair, i.e. XPC, XPD, XRCC1, and XRCC3, tended to influence the ICS. In order to find the combination of factors, on both protein and gene levels, with the highest correlation to ICS, a multivariate statistical calculation was performed. Our results indicate that SNPs in DNA repair genes (XRCC3241 and XPD751) influence the ICS and together with the expression of EGFR, Hsp70, Bax, and Bcl-2, they could predict the cisplatin sensitivity of head and neck cancer cell lines (r=0.614, p≤0.001).

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October 2009
Volume 24 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

2015 Impact Factor: 2.348
Ranked #22/123 Medicine Research and Experimental
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APA
Farnebo, L., Jedlinski, A., Ansell, A., Vainikka, L., Thunell, L.K., Grénman, R. ... Roberg, K. (2009). Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines. International Journal of Molecular Medicine, 24, 549-556. https://doi.org/10.3892/ijmm_00000264
MLA
Farnebo, L., Jedlinski, A., Ansell, A., Vainikka, L., Thunell, L. K., Grénman, R., Johansson, A., Roberg, K."Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines". International Journal of Molecular Medicine 24.4 (2009): 549-556.
Chicago
Farnebo, L., Jedlinski, A., Ansell, A., Vainikka, L., Thunell, L. K., Grénman, R., Johansson, A., Roberg, K."Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines". International Journal of Molecular Medicine 24, no. 4 (2009): 549-556. https://doi.org/10.3892/ijmm_00000264