PMID- 28679769
OWN - NLM
STAT- MEDLINE
DCOM- 20180717
LR  - 20200117
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 23
IP  - 19
DP  - 2017 Oct 1
TI  - Downregulation of Human Endogenous Retrovirus Type K (HERV-K) Viral env RNA in 
      Pancreatic Cancer Cells Decreases Cell Proliferation and Tumor Growth.
PG  - 5892-5911
LID - 10.1158/1078-0432.CCR-17-0001 [doi]
AB  - Purpose: We investigated the role of the human endogenous retrovirus type K 
      (HERV-K) envelope (env) gene in pancreatic cancer.Experimental Design: shRNA was 
      employed to knockdown (KD) the expression of HERV-K in pancreatic cancer 
      cells.Results: HERV-K env expression was detected in seven pancreatic cancer cell 
      lines and in 80% of pancreatic cancer patient biopsies, but not in two normal 
      pancreatic cell lines or uninvolved normal tissues. A new HERV-K splice variant 
      was discovered in several pancreatic cancer cell lines. Reverse transcriptase 
      activity and virus-like particles were observed in culture media supernatant 
      obtained from Panc-1 and Panc-2 cells. HERV-K viral RNA levels and anti-HERV-K 
      antibody titers were significantly higher in pancreatic cancer patient sera (N = 
      106) than in normal donor sera (N = 40). Importantly, the in vitro and in vivo 
      growth rates of three pancreatic cancer cell lines were significantly reduced 
      after HERV-K KD by shRNA targeting HERV-K env, and there was reduced metastasis 
      to lung after treatment. RNA-Seq results revealed changes in gene expression 
      after HERV-K env KD, including RAS and TP53. Furthermore, downregulation of 
      HERV-K Env protein expression by shRNA also resulted in decreased expression of 
      RAS, p-ERK, p-RSK, and p-AKT in several pancreatic cancer cells or 
      tumors.Conclusions: These results demonstrate that HERV-K influences signal 
      transduction via the RAS-ERK-RSK pathway in pancreatic cancer. Our data highlight 
      the potentially important role of HERV-K in tumorigenesis and progression of 
      pancreatic cancer, and indicate that HERV-K viral proteins may be attractive 
      biomarkers and/or tumor-associated antigens, as well as potentially useful 
      targets for detection, diagnosis, and immunotherapy of pancreatic cancer. Clin 
      Cancer Res; 23(19); 5892-911. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Li, Ming
AU  - Li M
AD  - Viral Oncology Program, Center for Cancer and Metabolism, SRI International, 
      Menlo Park, California.
FAU - Radvanyi, Laszlo
AU  - Radvanyi L
AD  - EMD Serono Research and Development Institute, Billerica, Massachusetts.
FAU - Yin, Bingnan
AU  - Yin B
AD  - Department of Inflammation and Epigenetics, Methodist Research Institute, 
      Houston, Texas.
FAU - Rycaj, Kiera
AU  - Rycaj K
FAU - Li, Jia
AU  - Li J
AD  - Viral Oncology Program, Center for Cancer and Metabolism, SRI International, 
      Menlo Park, California.
FAU - Chivukula, Raghavender
AU  - Chivukula R
AD  - Viral Oncology Program, Center for Cancer and Metabolism, SRI International, 
      Menlo Park, California.
FAU - Lin, Kevin
AU  - Lin K
AD  - Department of Epigenetics and Molecular Carcinogenesis, Science Park, the 
      University of Texas MD Anderson Cancer Center, Smithville, Texas.
FAU - Lu, Yue
AU  - Lu Y
AD  - Department of Epigenetics and Molecular Carcinogenesis, Science Park, the 
      University of Texas MD Anderson Cancer Center, Smithville, Texas.
FAU - Shen, JianJun
AU  - Shen J
AD  - Department of Epigenetics and Molecular Carcinogenesis, Science Park, the 
      University of Texas MD Anderson Cancer Center, Smithville, Texas.
FAU - Chang, David Z
AU  - Chang DZ
AD  - Virginia Oncology Associates, Newport News, Virginia.
FAU - Li, Donghui
AU  - Li D
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Johanning, Gary L
AU  - Johanning GL
AD  - Viral Oncology Program, Center for Cancer and Metabolism, SRI International, 
      Menlo Park, California.
FAU - Wang-Johanning, Feng
AU  - Wang-Johanning F
AD  - Viral Oncology Program, Center for Cancer and Metabolism, SRI International, 
      Menlo Park, California. feng.wang-johanning@sri.com.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170705
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Viral Envelope Proteins)
SB  - IM
EIN - Clin Cancer Res. 2019 May 1;25(9):2936. Rycaj, Kiera [added]. PMID: 31043384
MH  - Carcinogenesis/*genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Endogenous Retroviruses/*genetics/pathogenicity
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Expression Regulation, Viral
MH  - Gene Knockdown Techniques
MH  - Host-Pathogen Interactions/genetics
MH  - Humans
MH  - Pancreatic Neoplasms/*genetics/pathology/virology
MH  - RNA, Small Interfering/genetics
MH  - Recombinant Fusion Proteins/genetics
MH  - Signal Transduction/genetics
MH  - Viral Envelope Proteins/*genetics
PMC - PMC5777511
MID - NIHMS891106
EDAT- 2017/07/07 06:00
MHDA- 2018/07/18 06:00
PMCR- 2018/04/01
CRDT- 2017/07/07 06:00
PHST- 2017/01/03 00:00 [received]
PHST- 2017/05/09 00:00 [revised]
PHST- 2017/06/29 00:00 [accepted]
PHST- 2017/07/07 06:00 [pubmed]
PHST- 2018/07/18 06:00 [medline]
PHST- 2017/07/07 06:00 [entrez]
PHST- 2018/04/01 00:00 [pmc-release]
AID - 1078-0432.CCR-17-0001 [pii]
AID - 10.1158/1078-0432.CCR-17-0001 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2017 Oct 1;23(19):5892-5911. doi: 10.1158/1078-0432.CCR-17-0001. 
      Epub 2017 Jul 5.