PMID- 18339874
OWN - NLM
STAT- MEDLINE
DCOM- 20080409
LR  - 20211203
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 68
IP  - 6
DP  - 2008 Mar 15
TI  - Mammalian target of rapamycin repression by 3,3'-diindolylmethane inhibits 
      invasion and angiogenesis in platelet-derived growth factor-D-overexpressing PC3 
      cells.
PG  - 1927-34
LID - 10.1158/0008-5472.CAN-07-3241 [doi]
AB  - Platelet-derived growth factor-D (PDGF-D) is a newly recognized growth factor 
      known to regulate many cellular processes, including cell proliferation, 
      transformation, invasion, and angiogenesis. Recent studies have shown that PDGF-D 
      and its cognate receptor PDGFR-beta are expressed in prostate tumor tissues, 
      suggesting that PDGF-D might play an important role in the development and 
      progression of prostate cancer. However, the biological role of PDGF-D in 
      tumorigenesis remains elusive. In this study, we found that PDGF-D-overexpressing 
      PC3 cells (PC3 cells stably transfected with PDGF-D cDNA and referred to as PC3 
      PDGF-D) exhibited a rapid growth rate and enhanced cell invasion that was 
      associated with the activation of mammalian target of rapamycin (mTOR) and 
      reduced Akt activity. Rapamycin repressed mTOR activity and concomitantly 
      resulted in the activation of Akt, which could attenuate the therapeutic effects 
      of mTOR inhibitors. In contrast, B-DIM (BR-DIM from Bioresponse, Inc.; a 
      chemopreventive agent) significantly inhibited both mTOR and Akt in PC3 PDGF-D 
      cells, which were correlated with decreased cell proliferation and invasion. 
      Moreover, conditioned medium from PC3 PDGF-D cells significantly increased the 
      tube formation of human umbilical vein endothelial cells, which was inhibited by 
      B-DIM treatment concomitant with reduced full-length and active form of PDGF-D. 
      Our results suggest that B-DIM could serve as a novel and efficient 
      chemopreventive and/or therapeutic agent by inactivation of both mTOR and Akt 
      activity in PDGF-D-overexpressing prostate cancer.
FAU - Kong, Dejuan
AU  - Kong D
AD  - Department of Pathology, Karmanos Cancer Institute, Wayne State University School 
      of Medicine, Detroit, MI 48201, USA.
FAU - Banerjee, Sanjeev
AU  - Banerjee S
FAU - Huang, Wei
AU  - Huang W
FAU - Li, Yiwei
AU  - Li Y
FAU - Wang, Zhiwei
AU  - Wang Z
FAU - Kim, Hyeong-Reh Choi
AU  - Kim HR
FAU - Sarkar, Fazlul H
AU  - Sarkar FH
LA  - eng
GR  - R01 CA108535/CA/NCI NIH HHS/United States
GR  - R01 CA132794/CA/NCI NIH HHS/United States
GR  - R01 CA164318/CA/NCI NIH HHS/United States
GR  - 5R01CA108535-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Indoles)
RN  - 0 (Lymphokines)
RN  - 0 (PDGFD protein, human)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - SSZ9HQT61Z (3,3'-diindolylmethane)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Growth Processes/drug effects
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Lymphokines/*biosynthesis/genetics/pharmacology
MH  - Male
MH  - Neoplasm Invasiveness
MH  - Neovascularization, Pathologic/drug therapy/enzymology
MH  - Platelet-Derived Growth Factor/*biosynthesis/genetics/pharmacology
MH  - Prostatic Neoplasms/blood supply/*drug therapy/metabolism/pathology
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Protein Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Transfection
MH  - Up-Regulation/drug effects
PMC - PMC3757473
MID - NIHMS510652
EDAT- 2008/03/15 09:00
MHDA- 2008/04/10 09:00
PMCR- 2013/08/30
CRDT- 2008/03/15 09:00
PHST- 2008/03/15 09:00 [pubmed]
PHST- 2008/04/10 09:00 [medline]
PHST- 2008/03/15 09:00 [entrez]
PHST- 2013/08/30 00:00 [pmc-release]
AID - 68/6/1927 [pii]
AID - 10.1158/0008-5472.CAN-07-3241 [doi]
PST - ppublish
SO  - Cancer Res. 2008 Mar 15;68(6):1927-34. doi: 10.1158/0008-5472.CAN-07-3241.