PMID- 25176506
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20211021
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 32
IP  - 5
DP  - 2014 Nov
TI  - Targeting of the beta6 gene to suppress degradation of ECM via inactivation of the 
      MAPK pathway in breast adenocarcinoma cells.
PG  - 1787-95
LID - 10.3892/or.2014.3419 [doi]
AB  - Integrin alphanubeta6 has emerged as a potential novel target for anticancer and plays a 
      major role in promoting malignant tumor progression. Recent studies indicate that 
      integrin alphanubeta6 occurs in many cancers. However, whether and how alphanubeta6 is regulated 
      by genetic and epigenetic mechanisms in breast cancer remain unknown. In the 
      present study, two different short hairpin RNAs (shRNAs) targeting the beta6 gene 
      were designed and constructed into pSUPER, respectively, which were transfected 
      into the MCF-7 human breast adenocarcinoma cell line. The beta6-shRNA stably 
      transfected cells were successfully established, and significant lower levels of 
      alphanubeta6 mRNA and protein expression were confirmed. Furthermore, inhibition of 
      integrin alphanubeta6 markedly downregulated the expression of matrix 
      metalloproteinase-9 (MMP-9), matrix metalloproteinase-3 (MMP-3) and urokinase 
      plasminogen activator (uPA) in tumor conditioned medium. Furthermore, 
      beta6-shRNA-mediated silencing of the alphanubeta6 gene obviously decreased the expression 
      of ERK1/2. In particular, supression of integrin alphanubeta6 caused significant 
      downregulation of the degradation of basement membrane type IV collagen secretion 
      via modulation of the plasminogen activation cascade. Our results thus indicate 
      that alphanubeta6 plays a fundamental role in promoting invasion and growth of breast 
      adenocarcinoma cells. Taken together, this study revealed that targeting of the 
      beta6 gene by RNA interference (RNAi) could efficiently downregulate alphanubeta6 expression 
      and suppress the ERK1/2-dependent extracellular matrix degradation in vitro, 
      which is dependent upon inactivation of the mitogen-activated protein 
      kinase (MAPK) pathway. These findings may offer a useful therapeutic approach to 
      block invasion and migration of breast cancer cells.
FAU - Zhang, Yuhua
AU  - Zhang Y
AD  - Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Wei, Lijing
AU  - Wei L
AD  - Department of Urology, Shandong Provincial Hospital, Jinan, Shandong 250021, P.R. 
      China.
FAU - Yu, Jin
AU  - Yu J
AD  - Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Li, Guang
AU  - Li G
AD  - Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Zhang, Xiuru
AU  - Zhang X
AD  - Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Wang, Anliu
AU  - Wang A
AD  - Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - He, Yanjiao
AU  - He Y
AD  - Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Li, Hongli
AU  - Li H
AD  - Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Yin, Deling
AU  - Yin D
AD  - Department of Internal Medicine, Department of Pharmacology, James H. Quillen 
      College of Medicine, East Tennessee State University, Johnson City, TN 37614, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140820
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Integrin beta Chains)
RN  - 0 (Integrins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (integrin alphavbeta6)
RN  - 0 (integrin beta6)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.35 (MMP9 protein, human)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adenocarcinoma/genetics/*metabolism
MH  - Antigens, Neoplasm/genetics/*metabolism
MH  - Breast Neoplasms/genetics/*metabolism
MH  - Extracellular Matrix/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Targeting/methods
MH  - Humans
MH  - Integrin beta Chains/*genetics/metabolism
MH  - Integrins/genetics/*metabolism
MH  - MAP Kinase Signaling System
MH  - MCF-7 Cells
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - RNA, Small Interfering/*metabolism
MH  - Urokinase-Type Plasminogen Activator/genetics/metabolism
PMC - PMC4203328
EDAT- 2014/09/02 06:00
MHDA- 2015/10/27 06:00
PMCR- 2014/08/20
CRDT- 2014/09/02 06:00
PHST- 2014/05/01 00:00 [received]
PHST- 2014/07/30 00:00 [accepted]
PHST- 2014/09/02 06:00 [entrez]
PHST- 2014/09/02 06:00 [pubmed]
PHST- 2015/10/27 06:00 [medline]
PHST- 2014/08/20 00:00 [pmc-release]
AID - or-32-05-1787 [pii]
AID - 10.3892/or.2014.3419 [doi]
PST - ppublish
SO  - Oncol Rep. 2014 Nov;32(5):1787-95. doi: 10.3892/or.2014.3419. Epub 2014 Aug 20.