TY - JOUR
T1 - Attenuated XPC expression is not associated with impaired DNA repair in bladder cancer
AU - Naipal, Kishan A.T.
AU - Raams, Anja
AU - Bruens, Serena T.
AU - Brandsma, Inger
AU - Verkaik, Nicole S.
AU - Jaspers, Nicolaas G.J.
AU - Hoeijmakers, Jan H.J.
AU - Van Leenders, Geert J.L.H.
AU - Pothof, Joris
AU - Kanaar, Roland
AU - Boormans, Joost
AU - Van Gent, Dik C.
N1 - Publisher Copyright:
© 2015 Naipal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84957824890&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0126029
DO - 10.1371/journal.pone.0126029
M3 - Article
C2 - 25927440
AN - SCOPUS:84957824890
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e0126029
ER -