Attenuated XPC expression is not associated with impaired DNA repair in bladder cancer.
Bladder cancer has a high incidence with significant morbidity and mortality. Attenuated expression of the DNA damage response protein Xeroderma Pigmentosum complementation group C (XPC) has been described in bladder cancer. XPC plays an essential role as the main initiator and damage-detector in global genome nucleotide excision repair (NER) of UV-induced lesions, bulky DNA adducts and intrastrand crosslinks, such as those made by the chemotherapeutic agent Cisplatin. Hence, XPC protein might be an informative biomarker to guide personalized therapy strategies in a subset of bladder cancer cases. Therefore, we measured the XPC protein expression level and functional NER activity of 36 bladder tumors in a standardized manner. We optimized conditions for dissociation and in vitro culture of primary bladder cancer cells and confirmed attenuated XPC expression in approximately 40% of the tumors. However, NER activity was similar to co-cultured wild type cells in all but one of 36 bladder tumors. We conclude, that (i) functional NER deficiency is a relatively rare phenomenon in bladder cancer and (ii) XPC protein levels are not useful as biomarker for NER activity in these tumors.
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Kishan A T
KA
Naipal
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Anja
A
Raams
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Serena T
ST
Bruens
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Inger
I
Brandsma
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Nicole S
NS
Verkaik
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Nicolaas G J
NG
Jaspers
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Jan H J
JH
Hoeijmakers
Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Geert J L H
GJ
van Leenders
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Joris
J
Pothof
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands; Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam, The Netherlands.
Roland
R
Kanaar
Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Joost
J
Boormans
Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Dik C
DC
van Gent
D004247:DNA / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins; C086984:XPC protein, human; D004247:DNA