PMID- 21465482
OWN - NLM
STAT- MEDLINE
DCOM- 20120130
LR  - 20211020
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 227
IP  - 2
DP  - 2012 Feb
TI  - Insulin-like growth factor 1 stimulation of androgen receptor activity requires 
      beta(1A) integrins.
PG  - 751-8
LID - 10.1002/jcp.22784 [doi]
AB  - Despite the findings that beta1 integrins play a vital role in the regulation of 
      cell proliferation and survival, the mechanisms through which they operate and 
      lead to cancer progression remain elusive. Previously, our laboratory has shown 
      that beta(1A) integrins support insulin-like growth factor 1 (IGFI)-mediated 
      mitogenic and transforming activities. Here, we report that beta(1A) integrins 
      regulate basal levels of IGF-IR, although they are not critical for maintaining 
      cancer cell morphology. Upon transfection of beta(1A) siRNA and consequent 
      downregulation of IGF-IR, we show inhibition of anchorage-independent growth of 
      prostate cancer cells, a function which is dependent on IGF-IR expression. In 
      addition, we demonstrate that IGFI-mediated activation of androgen receptor (AR), 
      known to occur in prostate cancer cells, requires expression of beta(1A) integrins 
      as evaluated by luciferase reporter assays and immunoblotting analysis. Since 
      beta(1A) integrin levels are increased by R1881 or dihydrotestosterone (DHT), our 
      results imply that beta(1A) integrins support an androgen-enhanced feedback loop 
      that regulates the expression of IGF-IR. beta(1A) integrins also regulate inducible 
      levels of IGF-IR in cells stimulated by androgen or by a combination of androgen 
      and IGFI, as evaluated by flow cytometric analysis and immunoblotting. 
      Furthermore, upon transfection of beta(1A) siRNA and consequent downregulation of 
      IGF-IR, neither activation of AKT, an effector of IGF-IR, nor AR levels are 
      affected. We conclude that beta(1A) integrin expression is critical for maintaining 
      the regulatory crosstalk between IGF-IR and AR.
CI  - Copyright (c) 2011 Wiley Periodicals, Inc.
FAU - Sayeed, Aejaz
AU  - Sayeed A
AD  - Department of Cancer Biology, Prostate Cancer Discovery and Development Program, 
      Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
FAU - Alam, Naved
AU  - Alam N
FAU - Trerotola, Marco
AU  - Trerotola M
FAU - Languino, Lucia R
AU  - Languino LR
LA  - eng
GR  - R01 CA089720/CA/NCI NIH HHS/United States
GR  - P01 CA140043/CA/NCI NIH HHS/United States
GR  - R01 CA109874/CA/NCI NIH HHS/United States
GR  - R01 CA109874-06/CA/NCI NIH HHS/United States
GR  - P01 CA-140043/CA/NCI NIH HHS/United States
GR  - R01 CA-109874/CA/NCI NIH HHS/United States
GR  - P01 CA140043-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Androgens)
RN  - 0 (Integrin beta1)
RN  - 0 (Receptors, Androgen)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Androgens
MH  - Animals
MH  - Cell Line, Tumor
MH  - Feedback, Physiological/physiology
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Integrin beta1/genetics/*metabolism
MH  - Mice
MH  - Receptor, IGF Type 1/genetics/metabolism
MH  - Receptors, Androgen/*metabolism
MH  - Signal Transduction
PMC - PMC3195902
MID - NIHMS287348
EDAT- 2011/04/06 06:00
MHDA- 2012/01/31 06:00
PMCR- 2013/02/01
CRDT- 2011/04/06 06:00
PHST- 2011/04/06 06:00 [entrez]
PHST- 2011/04/06 06:00 [pubmed]
PHST- 2012/01/31 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - 10.1002/jcp.22784 [doi]
PST - ppublish
SO  - J Cell Physiol. 2012 Feb;227(2):751-8. doi: 10.1002/jcp.22784.