Human RecQL4 helicase plays critical roles in prostate carcinogenesis

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

SN - 0008-5472

VL - 70

SP - 9207

EP - 9217

JO - Cancer Research

JF - Cancer Research

IS - 22

ER -