PMID- 24504055
OWN - NLM
STAT- MEDLINE
DCOM- 20140429
LR  - 20211021
IS  - 1535-5667 (Electronic)
IS  - 0161-5505 (Print)
IS  - 0161-5505 (Linking)
VI  - 55
IP  - 3
DP  - 2014 Mar
TI  - Propranolol inhibits glucose metabolism and 18F-FDG uptake of breast cancer 
      through posttranscriptional downregulation of hexokinase-2.
PG  - 439-45
LID - 10.2967/jnumed.113.121327 [doi]
AB  - The advancement of breast cancer therapy is limited by the biologic behaviors of 
      cancer cells, such as metastasis and recurrence. beta-adrenoceptors (ADRB) are 
      reported to be associated with the biologic behaviors of breast cancer and may 
      influence glucose metabolism. Here, we sought to investigate the relationship 
      between the activation of ADRB and the expression of glucose transporter (GLUT)-1 
      and hexokinase (HK)-2 and to clarify the impact of ADRB on (18)F-FDG PET imaging 
      in breast cancer. METHODS: ADRB1/2 expression in 4T1, MDA-MB-231, and MCF-7 
      breast cancer cell lines was detected by Western blotting and immunofluorescence. 
      ADRB-dependent regulation of GLUT-1 and HK-2 was determined by in vitro 
      pharmacologic intervention. 4T1 breast cancer cells were treated with 
      phosphate-buffered saline, isoproterenol, or propranolol, and the transcription 
      and expression of GLUT-1 and HK-2 were measured by quantitative real-time 
      polymerase chain reaction (RT-PCR) and Western blotting, respectively. ADRB1/2 
      was, respectively, blocked by small-interfering RNA to investigate the direct 
      relationship between ADRB1/2 and HK-2. To evaluate the impact of ADRB on 
      (18)F-FDG PET imaging, BALB/c mice bearing 4T1 tumors were injected with 
      phosphate-buffered saline, isoproterenol, or propranolol, and (18)F-FDG PET 
      imaging was performed. The tumor-to-nontumor (T/NT) values of tumors and brown 
      adipose tissue were calculated by defining the liver as a reference. The in vivo 
      expression of GLUT-1 and HK-2 was observed by immunohistochemical analysis and 
      Western blotting. RESULTS: MDA-MB-231, MCF-7, and 4T1 breast cancer cells were 
      positive for ADRB1/2 expression. The protein expression and posttranscriptional 
      level of HK-2 were significantly decreased by treatment with propranolol in 
      vitro, whereas GLUT-1 expression was not significantly altered by pharmacologic 
      intervention. The expression of HK-2 could be reduced in ADRB2-blocked 4T1 cells. 
      Mice in the propranolol-treated group exhibited lower T/NT values for the tumors 
      and brown adipose tissue than the control group. Immunohistochemical analysis and 
      Western blotting revealed reduced HK-2 expression in the tumors of 
      propranolol-treated mice. CONCLUSION: The expression of HK-2 was regulated by the 
      activation of ADRB2 in 4T1 breast cancer cells primarily at the 
      posttranscriptional level. Additionally, propranolol prevented glucose metabolism 
      and (18)F-FDG PET imaging of 4T1 breast cancer tumors.
FAU - Kang, Fei
AU  - Kang F
AD  - Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, China.
FAU - Ma, Wenhui
AU  - Ma W
FAU - Ma, Xiaowei
AU  - Ma X
FAU - Shao, Yahui
AU  - Shao Y
FAU - Yang, Weidong
AU  - Yang W
FAU - Chen, Xiaoyuan
AU  - Chen X
FAU - Li, Liwen
AU  - Li L
FAU - Wang, Jing
AU  - Wang J
LA  - eng
GR  - ZIA EB000073-05/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140206
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - 0 (ADRB1 protein, human)
RN  - 0 (ADRB2 protein, human)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Receptors, Adrenergic, beta-1)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 9Y8NXQ24VQ (Propranolol)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Breast Neoplasms/diagnostic imaging/genetics/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Down-Regulation/*drug effects
MH  - Female
MH  - Fluorodeoxyglucose F18/*metabolism
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 1/metabolism
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Positron-Emission Tomography
MH  - Propranolol/*pharmacology
MH  - Receptors, Adrenergic, beta-1/genetics
MH  - Receptors, Adrenergic, beta-2/genetics
PMC - PMC4564063
MID - NIHMS720985
OTO - NOTNLM
OT  - 18F-FDG PET imaging
OT  - ADRB
OT  - glucose metabolism
OT  - hexokinase 2
OT  - propranolol
EDAT- 2014/02/08 06:00
MHDA- 2014/04/30 06:00
PMCR- 2015/09/09
CRDT- 2014/02/08 06:00
PHST- 2014/02/08 06:00 [entrez]
PHST- 2014/02/08 06:00 [pubmed]
PHST- 2014/04/30 06:00 [medline]
PHST- 2015/09/09 00:00 [pmc-release]
AID - jnumed.113.121327 [pii]
AID - 10.2967/jnumed.113.121327 [doi]
PST - ppublish
SO  - J Nucl Med. 2014 Mar;55(3):439-45. doi: 10.2967/jnumed.113.121327. Epub 2014 Feb 
      6.