Human RecQL4 helicase plays critical roles in prostate carcinogenesis
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Human RecQL4 helicase plays critical roles in prostate carcinogenesis. / Su, Yanrong; Meador, Jarah A; Calaf, Gloria M; Proietti De-Santis, Luca; Zhao, Yongliang; Bohr, Vilhelm A; Balajee, Adayabalam S.
In: Cancer Research, Vol. 70, No. 22, 15.11.2010, p. 9207-17.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human RecQL4 helicase plays critical roles in prostate carcinogenesis
AU - Su, Yanrong
AU - Meador, Jarah A
AU - Calaf, Gloria M
AU - Proietti De-Santis, Luca
AU - Zhao, Yongliang
AU - Bohr, Vilhelm A
AU - Balajee, Adayabalam S
N1 - Copyright © 2010 AACR.
PY - 2010/11/15
Y1 - 2010/11/15
N2 - Prostate cancer is the second leading cause of cancer-associated deaths among men in the western countries. Here, we report that human RecQL4 helicase, which is implicated in the pathogenesis of a subset of cancer-prone Rothmund-Thomson syndrome, is highly elevated in metastatic prostate cancer cell lines. Increased RecQL4 expression was also detected in human prostate tumor tissues as a function of tumor grade with the highest expression level in metastatic tumor samples, suggesting that RecQL4 may be a potential prognostic factor for advanced stage of prostate cancer. Transient and stable suppression of RecQL4 by small interfering RNA and short hairpin RNA vectors drastically reduced the growth and survival of metastatic prostate cancer cells, indicating that RecQL4 is a prosurvival factor for prostate cancer cells. RecQL4 suppression led to increased poly(ADP-ribose) polymerase (PARP) synthesis and RecQL4-suppressed prostate cancer cells underwent an extensive apoptotic death in a PARP-1-dependent manner. Most notably, RecQL4 knockdown in metastatic prostate cancer cells drastically reduced their cell invasiveness in vitro and tumorigenicity in vivo, showing that RecQL4 is essential for prostate cancer promotion. Observation of a direct interaction of retinoblastoma (Rb) and E2F1 proteins with RecQL4 promoter suggests that Rb-E2F1 pathway may regulate RecQL4 expression. Collectively, our study shows that RecQL4 is an essential factor for prostate carcinogenesis.
AB - Prostate cancer is the second leading cause of cancer-associated deaths among men in the western countries. Here, we report that human RecQL4 helicase, which is implicated in the pathogenesis of a subset of cancer-prone Rothmund-Thomson syndrome, is highly elevated in metastatic prostate cancer cell lines. Increased RecQL4 expression was also detected in human prostate tumor tissues as a function of tumor grade with the highest expression level in metastatic tumor samples, suggesting that RecQL4 may be a potential prognostic factor for advanced stage of prostate cancer. Transient and stable suppression of RecQL4 by small interfering RNA and short hairpin RNA vectors drastically reduced the growth and survival of metastatic prostate cancer cells, indicating that RecQL4 is a prosurvival factor for prostate cancer cells. RecQL4 suppression led to increased poly(ADP-ribose) polymerase (PARP) synthesis and RecQL4-suppressed prostate cancer cells underwent an extensive apoptotic death in a PARP-1-dependent manner. Most notably, RecQL4 knockdown in metastatic prostate cancer cells drastically reduced their cell invasiveness in vitro and tumorigenicity in vivo, showing that RecQL4 is essential for prostate cancer promotion. Observation of a direct interaction of retinoblastoma (Rb) and E2F1 proteins with RecQL4 promoter suggests that Rb-E2F1 pathway may regulate RecQL4 expression. Collectively, our study shows that RecQL4 is an essential factor for prostate carcinogenesis.
KW - Cell Line, Tumor
KW - Cell Movement
KW - Cell Proliferation
KW - Cell Survival
KW - Chromatin Immunoprecipitation
KW - DNA Damage
KW - E2F1 Transcription Factor
KW - Gene Expression Regulation, Enzymologic
KW - Gene Expression Regulation, Neoplastic
KW - Hela Cells
KW - Histone Deacetylase Inhibitors
KW - Humans
KW - Hydroxamic Acids
KW - Immunohistochemistry
KW - In Situ Hybridization, Fluorescence
KW - Male
KW - Promoter Regions, Genetic
KW - Prostatic Neoplasms
KW - Protein Binding
KW - RNA Interference
KW - RecQ Helicases
KW - Retinoblastoma Protein
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Up-Regulation
U2 - 10.1158/0008-5472.CAN-10-1743
DO - 10.1158/0008-5472.CAN-10-1743
M3 - Journal article
C2 - 21045146
VL - 70
SP - 9207
EP - 9217
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 22
ER -
ID: 33492310