PMID- 26452103
OWN - NLM
STAT- MEDLINE
DCOM- 20160920
LR  - 20181113
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 29
IP  - 12
DP  - 2015 Dec
TI  - Both IGF1R and INSR Knockdown Exert Antitumorigenic Effects in Prostate Cancer In 
      Vitro and In Vivo.
PG  - 1694-707
LID - 10.1210/me.2015-1073 [doi]
AB  - The IGF network with its main receptors IGF receptor 1 (IGF1R) and insulin 
      receptor (INSR) is of major importance for cancer initiation and progression. To 
      date, clinical studies targeting this network were disappointing and call for 
      thorough analysis of the IGF network in cancer models. We highlight the oncogenic 
      effects controlled by IGF1R and INSR in prostate cancer cells and show 
      similarities as well as differences after receptor knockdown (KD). In PC3 
      prostate cancer cells stably transduced with inducible short hairpin RNAs, 
      targeting IGF1R or INSR attenuated cell growth and proliferation ultimately 
      driving cells into apoptosis. IGF1R KD triggered rapid and strong 
      antiproliferative and proapoptotic responses, whereas these effects were less 
      pronounced and delayed after INSR KD. Down-regulation of the antiapoptotic 
      proteins myeloid cell leukemia-1 and survivin was observed in both KDs, whereas 
      IGF1R KD also attenuated expression of prosurvival proteins B cell lymphoma-2 and 
      B cell lymphoma-xL. Receptor KD induced cell death involved autophagy in 
      particular upon IGF1R KD; however, no difference in mitochondrial energy 
      metabolism was observed. In a mouse xenograft model, induction of IGF1R or INSR 
      KD after tumor establishment eradicated most of the tumors. After 20 days of 
      receptor KD, tumor cells were found only in 1/14 IGF1R and 3/14 INSR KD tumor 
      remnants. Collectively, our data underline the oncogenic functions of IGF1R and 
      INSR in prostate cancer namely growth, proliferation, and survival in vitro as 
      well as in vivo and identify myeloid cell leukemia-1 and survivin as important 
      mediators of inhibitory and apoptotic effects.
FAU - Ofer, Philipp
AU  - Ofer P
AD  - Division of Experimental Urology (P.O., I.H., I.E.E., H.K., P.M.), Department of 
      Urology, Medical University, 6020 Innsbruck, Austria; Division of Genetic 
      Epidemiology (B.S.), Department of Medical Genetics, Molecular and Clinical 
      Pharmacology, Medical University, 6020 Innsbruck, Austria; Department of Internal 
      Medicine IV (N.H.), Medical University, 6020 Innsbruck, Austria; and Division of 
      Molecular Pathophysiology (S.G.), Biocenter, Medical University, 6020 Innsbruck, 
      Austria.
FAU - Heidegger, Isabel
AU  - Heidegger I
AD  - Division of Experimental Urology (P.O., I.H., I.E.E., H.K., P.M.), Department of 
      Urology, Medical University, 6020 Innsbruck, Austria; Division of Genetic 
      Epidemiology (B.S.), Department of Medical Genetics, Molecular and Clinical 
      Pharmacology, Medical University, 6020 Innsbruck, Austria; Department of Internal 
      Medicine IV (N.H.), Medical University, 6020 Innsbruck, Austria; and Division of 
      Molecular Pathophysiology (S.G.), Biocenter, Medical University, 6020 Innsbruck, 
      Austria.
FAU - Eder, Iris E
AU  - Eder IE
AD  - Division of Experimental Urology (P.O., I.H., I.E.E., H.K., P.M.), Department of 
      Urology, Medical University, 6020 Innsbruck, Austria; Division of Genetic 
      Epidemiology (B.S.), Department of Medical Genetics, Molecular and Clinical 
      Pharmacology, Medical University, 6020 Innsbruck, Austria; Department of Internal 
      Medicine IV (N.H.), Medical University, 6020 Innsbruck, Austria; and Division of 
      Molecular Pathophysiology (S.G.), Biocenter, Medical University, 6020 Innsbruck, 
      Austria.
FAU - Schopf, Bernd
AU  - Schopf B
AD  - Division of Experimental Urology (P.O., I.H., I.E.E., H.K., P.M.), Department of 
      Urology, Medical University, 6020 Innsbruck, Austria; Division of Genetic 
      Epidemiology (B.S.), Department of Medical Genetics, Molecular and Clinical 
      Pharmacology, Medical University, 6020 Innsbruck, Austria; Department of Internal 
      Medicine IV (N.H.), Medical University, 6020 Innsbruck, Austria; and Division of 
      Molecular Pathophysiology (S.G.), Biocenter, Medical University, 6020 Innsbruck, 
      Austria.
FAU - Neuwirt, Hannes
AU  - Neuwirt H
AD  - Division of Experimental Urology (P.O., I.H., I.E.E., H.K., P.M.), Department of 
      Urology, Medical University, 6020 Innsbruck, Austria; Division of Genetic 
      Epidemiology (B.S.), Department of Medical Genetics, Molecular and Clinical 
      Pharmacology, Medical University, 6020 Innsbruck, Austria; Department of Internal 
      Medicine IV (N.H.), Medical University, 6020 Innsbruck, Austria; and Division of 
      Molecular Pathophysiology (S.G.), Biocenter, Medical University, 6020 Innsbruck, 
      Austria.
FAU - Geley, Stephan
AU  - Geley S
AD  - Division of Experimental Urology (P.O., I.H., I.E.E., H.K., P.M.), Department of 
      Urology, Medical University, 6020 Innsbruck, Austria; Division of Genetic 
      Epidemiology (B.S.), Department of Medical Genetics, Molecular and Clinical 
      Pharmacology, Medical University, 6020 Innsbruck, Austria; Department of Internal 
      Medicine IV (N.H.), Medical University, 6020 Innsbruck, Austria; and Division of 
      Molecular Pathophysiology (S.G.), Biocenter, Medical University, 6020 Innsbruck, 
      Austria.
FAU - Klocker, Helmut
AU  - Klocker H
AD  - Division of Experimental Urology (P.O., I.H., I.E.E., H.K., P.M.), Department of 
      Urology, Medical University, 6020 Innsbruck, Austria; Division of Genetic 
      Epidemiology (B.S.), Department of Medical Genetics, Molecular and Clinical 
      Pharmacology, Medical University, 6020 Innsbruck, Austria; Department of Internal 
      Medicine IV (N.H.), Medical University, 6020 Innsbruck, Austria; and Division of 
      Molecular Pathophysiology (S.G.), Biocenter, Medical University, 6020 Innsbruck, 
      Austria.
FAU - Massoner, Petra
AU  - Massoner P
AD  - Division of Experimental Urology (P.O., I.H., I.E.E., H.K., P.M.), Department of 
      Urology, Medical University, 6020 Innsbruck, Austria; Division of Genetic 
      Epidemiology (B.S.), Department of Medical Genetics, Molecular and Clinical 
      Pharmacology, Medical University, 6020 Innsbruck, Austria; Department of Internal 
      Medicine IV (N.H.), Medical University, 6020 Innsbruck, Austria; and Division of 
      Molecular Pathophysiology (S.G.), Biocenter, Medical University, 6020 Innsbruck, 
      Austria.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151009
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Antigens, CD)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.10.1 (INSR protein, human)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Animals
MH  - Antigens, CD/genetics/*metabolism
MH  - Apoptosis/genetics/physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics/physiology
MH  - Cell Survival/genetics/physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Prostatic Neoplasms/genetics/*metabolism
MH  - RNA, Small Interfering/genetics/physiology
MH  - Receptor, IGF Type 1/genetics/*metabolism
MH  - Receptor, Insulin/genetics/*metabolism
MH  - Signal Transduction/genetics/physiology
MH  - Xenograft Model Antitumor Assays
PMC - PMC4669362
EDAT- 2015/10/10 06:00
MHDA- 2016/09/22 06:00
PMCR- 2015/10/09
CRDT- 2015/10/10 06:00
PHST- 2015/10/10 06:00 [entrez]
PHST- 2015/10/10 06:00 [pubmed]
PHST- 2016/09/22 06:00 [medline]
PHST- 2015/10/09 00:00 [pmc-release]
AID - ME-15-1073 [pii]
AID - 10.1210/me.2015-1073 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2015 Dec;29(12):1694-707. doi: 10.1210/me.2015-1073. Epub 2015 
      Oct 9.