Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian carcinoma cells.

Li,Q; Ding,L; Yu,J J; Mu,C; Tsang,B; Bostick-Bruton,F; Reed,E

doi:10.3892/ijo.13.5.987

Nov 1998 Volume 13 Issue 5

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Nov 1998 Volume 13 Issue 5

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Article

Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian carcinoma cells.

Authors:
- Q Li
- L Ding
- J J Yu
- C Mu
- B Tsang
- F Bostick-Bruton
- E Reed
View Affiliations / Copyright

Affiliations: Medical Ovarian Cancer Section, Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA.
Pages: 987-1079
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Published online on: November 1, 1998

https://doi.org/10.3892/ijo.13.5.987
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Abstract

Nucleotide excision repair (NER) is the DNA repair pathway by which cisplatin-induced damage is removed from DNA in human cells. ERCC-1 is one of the essential proteins in NER, and is essential for life. Enhanced ERCC-1 expression has been associated with clinical and cellular resistance to cisplatin. We therefore carried out this study to investigate the effect of cisplatin on ERCC-1 protein expression in A2780/CP70 human ovarian cancer cells. Western blot analysis showed that ERCC-1 protein levels were increased to more than 3 times control after a 1 h cisplatin exposure to A2780/CP70 cells in culture. This increase was time- and concentration-dependent. The effect of cisplatin was maximal at 40 mM and peaked 24-48 h after exposure to the drug. These results extend our previous observations that ERCC-1 mRNA expression is induced by cisplatin in this system. TPA, a known AP-1 activator and tumor-promoting phorbol ester, also induced ERCC-1 protein to the same extent as cisplatin, but did not synergize with cisplatin in this regard. These findings suggest that ERCC-1 gene up-regulation in these cells can result through a DNA damage-response pathway, or through the induction of AP-1 activity, independent of the occurrence of DNA damage.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian carcinoma cells.

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Abstract

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