TY - JOUR
T1 - The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation
AU - Mendoza-Maldonado, Ramiro
AU - Faoro, Valentina
AU - Bajpai, Sailesh
AU - Berti, Matteo
AU - Odreman, Federico
AU - Vindigni, Marco
AU - Ius, Tamara
AU - Ghasemian, Abdollah
AU - Bonin, Serena
AU - Skrap, Miran
AU - Stanta, Giorgio
AU - Vindigni, Alessandro
N1 - Funding Information:
The assistance of Mr. Gianluca Triolo is the growth and maintenance of human cell lines is gratefully acknowledged. This work was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC) to A.V [AIRC5088].
PY - 2011/7/13
Y1 - 2011/7/13
N2 - Background: RecQ helicases play an essential role in the maintenance of genome stability. In humans, loss of RecQ helicase function is linked with predisposition to cancer and/or premature ageing. Current data show that the specific depletion of the human RECQ1 helicase leads to mitotic catastrophe in cancer cells and inhibition of tumor growth in mice.Results: Here, we show that RECQ1 is highly expressed in various types of solid tumors. However, only in the case of brain gliomas, the high expression of RECQ1 in glioblastoma tissues is paralleled by a lower expression in the control samples due to the poor expression of RECQ1 in non-dividing tissues. This conclusion is validated by immunohistochemical analysis of a tissue microarray containing 63 primary glioblastomas and 19 perilesional tissue samples, as control. We also show that acute depletion of RECQ1 by RNAi results in a significant reduction of cellular proliferation, perturbation of S-phase progression, and spontaneous γ-H2AX foci formation in T98G and U-87 glioblastoma cells. Moreover, RECQ1 depleted T98G and U-87 cells are hypersensitive to HU or temozolomide treatment.Conclusions: Collectively, these results indicate that RECQ1 has a unique and important role in the maintenance of genome integrity. Our results also suggest that RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas.
AB - Background: RecQ helicases play an essential role in the maintenance of genome stability. In humans, loss of RecQ helicase function is linked with predisposition to cancer and/or premature ageing. Current data show that the specific depletion of the human RECQ1 helicase leads to mitotic catastrophe in cancer cells and inhibition of tumor growth in mice.Results: Here, we show that RECQ1 is highly expressed in various types of solid tumors. However, only in the case of brain gliomas, the high expression of RECQ1 in glioblastoma tissues is paralleled by a lower expression in the control samples due to the poor expression of RECQ1 in non-dividing tissues. This conclusion is validated by immunohistochemical analysis of a tissue microarray containing 63 primary glioblastomas and 19 perilesional tissue samples, as control. We also show that acute depletion of RECQ1 by RNAi results in a significant reduction of cellular proliferation, perturbation of S-phase progression, and spontaneous γ-H2AX foci formation in T98G and U-87 glioblastoma cells. Moreover, RECQ1 depleted T98G and U-87 cells are hypersensitive to HU or temozolomide treatment.Conclusions: Collectively, these results indicate that RECQ1 has a unique and important role in the maintenance of genome integrity. Our results also suggest that RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas.
UR - http://www.scopus.com/inward/record.url?scp=79960111219&partnerID=8YFLogxK
U2 - 10.1186/1476-4598-10-83
DO - 10.1186/1476-4598-10-83
M3 - Article
C2 - 21752281
AN - SCOPUS:79960111219
SN - 1476-4598
VL - 10
JO - Molecular Cancer
JF - Molecular Cancer
M1 - 83
ER -