PMID- 25628930
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150128
LR  - 20201001
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 5
IP  - 1
DP  - 2015
TI  - Characterization of 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine at androgen 
      receptor: mechanistic support for its role in prostate cancer.
PG  - 191-200
AB  - 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) is a dietary mutagenic 
      carcinogen that has been shown not only to induce the formation of DNA adducts, 
      but is capable of inducing tumors in the colon, mammary, and prostate glands. The 
      normal development and maturation of the prostate gland, as well as early 
      progression of prostate cancer, is dependent on androgens acting on the androgen 
      receptor (AR). The actual mechanism by which PhIP interacts with our biological 
      system and its potential interaction at the AR has yet to be fully defined. Here, 
      we describe our work in evaluating the molecular events associated with 
      PhIP-mediated disruption of AR function in LNCaP human prostate cancer cells. We 
      demonstrate, by molecular docking simulation, that PhIP and its metabolite can 
      bind to the ligand-binding domain (LBD). The binding competes with 
      dihydrotestosterone (DHT) in the native AR binding cavity of the receptor. In 
      vitro assays show that PhIP increase AR protein expression in LNCaP cells and 
      alters its responsiveness through PSA protein and mRNA expression. We propose 
      that the mechanism for the tissue-specific carcinogenicity seen in the rat 
      prostate tumors and the presumptive human prostate cancer associated with the 
      consumption of well-done meat may be mediated by this receptor activation. Our 
      results indicate that PhIP may play an important role in modifications of AR 
      function.
FAU - Glass-Holmes, Mashunte
AU  - Glass-Holmes M
AD  - Florida A&M University College of Pharmacy & Pharmaceutical Sciences Dyson 
      Pharmacy Building, Suite 201 1520 S. Martin Luther King Jr. Blvd Tallahassee, FL 
      32307.
FAU - Aguilar, Byron J
AU  - Aguilar BJ
AD  - Florida A&M University College of Pharmacy & Pharmaceutical Sciences Dyson 
      Pharmacy Building, Suite 201 1520 S. Martin Luther King Jr. Blvd Tallahassee, FL 
      32307.
FAU - Gragg, Richard D 3rd
AU  - Gragg RD 3rd
AD  - Florida A&M University College of Pharmacy & Pharmaceutical Sciences Dyson 
      Pharmacy Building, Suite 201 1520 S. Martin Luther King Jr. Blvd Tallahassee, FL 
      32307.
FAU - Darling-Reed, Selina
AU  - Darling-Reed S
AD  - Florida A&M University College of Pharmacy & Pharmaceutical Sciences Dyson 
      Pharmacy Building, Suite 201 1520 S. Martin Luther King Jr. Blvd Tallahassee, FL 
      32307.
FAU - Goodman, Carl B
AU  - Goodman CB
AD  - Florida A&M University College of Pharmacy & Pharmaceutical Sciences Dyson 
      Pharmacy Building, Suite 201 1520 S. Martin Luther King Jr. Blvd Tallahassee, FL 
      32307.
LA  - eng
GR  - G12 MD007582/MD/NIMHD NIH HHS/United States
GR  - P20 MD006738/MD/NIMHD NIH HHS/United States
PT  - Journal Article
DEP - 20141215
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC4300711
OTO - NOTNLM
OT  - 2-amino-1-methyl-6-phenylimidazo[4
OT  - 5b]pyridine (PhIP)
OT  - dietary carcinogenesis
OT  - molecular modeling
OT  - prostate cancer
EDAT- 2015/01/30 06:00
MHDA- 2015/01/30 06:01
PMCR- 2014/12/15
CRDT- 2015/01/29 06:00
PHST- 2014/05/07 00:00 [received]
PHST- 2014/11/25 00:00 [accepted]
PHST- 2015/01/29 06:00 [entrez]
PHST- 2015/01/30 06:00 [pubmed]
PHST- 2015/01/30 06:01 [medline]
PHST- 2014/12/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2014 Dec 15;5(1):191-200. eCollection 2015.