PMID- 33939664
OWN - NLM
STAT- MEDLINE
DCOM- 20220119
LR  - 20230822
IS  - 1536-4828 (Electronic)
IS  - 0885-3177 (Print)
IS  - 0885-3177 (Linking)
VI  - 50
IP  - 4
DP  - 2021 Apr 1
TI  - Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells.
PG  - 524-528
LID - 10.1097/MPA.0000000000001790 [doi]
AB  - OBJECTIVES: Obesity, a risk factor for pancreatic adenocarcinoma (PDAC), is often 
      accompanied by a systemic increase in lipopolysaccharide (LPS; metabolic 
      endotoxemia), which is thought to mediate obesity-associated inflammation. 
      However, the direct effects of LPS on PDAC cells are poorly understood. METHODS: 
      The expression of toll-like receptor 4, the receptor for LPS, was confirmed in 
      PDAC cell lines. AsPC-1 and PANC-1 cells were exposed to LPS, and differential 
      gene expression was determined by RNA sequencing. The activation of the 
      phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of 
      rapamycin (mTOR) pathway by LPS in PDAC cells was assessed by Western blotting. 
      RESULTS: The expression of toll-like receptor 4 was confirmed in all PDAC cell 
      lines. The exposure to LPS led to differential expression of 3083 genes (426 
      >/=5-fold) in AsPC-1 and 2584 genes (339 >/=5-fold) in PANC-1. A top canonical 
      pathway affected by LPS in both cell lines was PI3K/Akt/mTOR. Western blotting 
      confirmed activation of this pathway as measured by phosphorylation of the 
      ribosomal protein S6 and Akt. CONCLUSIONS: The exposure of PDAC cells to LPS led 
      to differential gene expression. A top canonical pathway was PI3K/Akt/mTOR, a 
      known oncogenic driver. Our findings provided evidence that LPS can directly 
      induce differential gene expression in PDAC cells.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Massoumi, Roxanne L
AU  - Massoumi RL
AD  - From the Department of Surgery, David Geffen School of Medicine at UCLA, Los 
      Angeles, CA.
FAU - Teper, Yaroslav
AU  - Teper Y
FAU - Ako, Soichiro
AU  - Ako S
FAU - Ye, Linda
AU  - Ye L
FAU - Wang, Elena
AU  - Wang E
FAU - Hines, O Joe
AU  - Hines OJ
FAU - Eibl, Guido
AU  - Eibl G
LA  - eng
GR  - P01 CA236585/CA/NCI NIH HHS/United States
GR  - P30 CA016042/CA/NCI NIH HHS/United States
GR  - T32 DK007180/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pancreas
JT  - Pancreas
JID - 8608542
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Blotting, Western
MH  - Carcinoma, Pancreatic Ductal/*genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Lipopolysaccharides/*pharmacology
MH  - Pancreatic Neoplasms/*genetics/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA-Seq/methods
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Toll-Like Receptor 4/genetics/metabolism
MH  - Transcriptome/*drug effects
PMC - PMC8097724
MID - NIHMS1676638
COIS- The authors declare no conflict of interest.
EDAT- 2021/05/04 06:00
MHDA- 2022/01/20 06:00
PMCR- 2022/04/01
CRDT- 2021/05/03 17:32
PHST- 2021/05/03 17:32 [entrez]
PHST- 2021/05/04 06:00 [pubmed]
PHST- 2022/01/20 06:00 [medline]
PHST- 2022/04/01 00:00 [pmc-release]
AID - 00006676-202104000-00007 [pii]
AID - 10.1097/MPA.0000000000001790 [doi]
PST - ppublish
SO  - Pancreas. 2021 Apr 1;50(4):524-528. doi: 10.1097/MPA.0000000000001790.