PMID- 9918209
OWN - NLM
STAT- MEDLINE
DCOM- 19990324
LR  - 20220330
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 5
IP  - 1
DP  - 1999 Jan
TI  - The nuclear factor-kappa B RelA transcription factor is constitutively activated 
      in human pancreatic adenocarcinoma cells.
PG  - 119-27
AB  - Pancreatic adenocarcinoma is a leading cause of adult cancer mortality in the 
      United States. Recent studies have revealed that point mutation of the K-ras 
      oncogene is a common event in pancreatic cancer, and oncogenesis mediated by Ras 
      may also involve activation of Rel/nuclear factor (NF)-kappa B transcription 
      factors. Furthermore, the c-rel member of Rel/NF-kappa B transcription factor 
      family was first identified as a cellular homologue of the v-rel oncogene, 
      suggesting that other members of the Rel/NF-kappa B family are potentially 
      oncogenes. We therefore investigated the possibility that Rel/NF-kappa B 
      transcription factors are activated in pancreatic cancer. Immunohistochemical 
      analysis, Western blot and Northern blot analysis, electrophoretic mobility shift 
      assays, and chloramphenicol acetyltransferase assays were performed to determine 
      RelA activity in human pancreatic adenocarcinomas and normal tissues and 
      nontumorigenic or tumorigenic cell lines. RelA, the p65 subunit of NF-kappa B, 
      was constitutively activated in approximately 67% (16 of 24) of pancreatic 
      adenocarcinomas but not in normal pancreatic tissues. Constitutive RelA activity 
      was also detected in 9 of 11 human pancreatic tumor cell lines but not in 
      nontumorigenic Syrian golden hamster cell lines. I kappa B alpha, a previously 
      identified NF-kappa B-inducible gene, was overexpressed in human pancreatic tumor 
      tissues and cell lines, and RelA activation could be inhibited by curcumin and 
      dominant-negative mutants of I kappa B alpha, raf, and MEKK1. This is the first 
      report demonstrating constitutive activation of RelA in nonlymphoid human cancer. 
      These data are consistent with the possibility that RelA is constitutively 
      activated by the upstream signaling pathway involving Ras and mitogen-activated 
      protein kinases in pancreatic tumor cells. Constitutive RelA activity may play a 
      key role in pancreatic tumorigenesis through activation of its downstream target 
      genes.
FAU - Wang, W
AU  - Wang W
AD  - Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer 
      Center, Houston 77030, USA.
FAU - Abbruzzese, J L
AU  - Abbruzzese JL
FAU - Evans, D B
AU  - Evans DB
FAU - Larry, L
AU  - Larry L
FAU - Cleary, K R
AU  - Cleary KR
FAU - Chiao, P J
AU  - Chiao PJ
LA  - eng
GR  - CA73675-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
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 (DNA, Neoplasm)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor RelA)
SB  - IM
MH  - Adenocarcinoma/genetics/*metabolism
MH  - Adult
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cricetinae
MH  - DNA, Neoplasm/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, ras
MH  - Humans
MH  - Immunohistochemistry
MH  - Mesocricetus
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism
MH  - Pancreatic Neoplasms/genetics/*metabolism
MH  - Point Mutation
MH  - Transcription Factor RelA
MH  - Tumor Cells, Cultured
EDAT- 1999/01/26 00:00
MHDA- 1999/01/26 00:01
CRDT- 1999/01/26 00:00
PHST- 1999/01/26 00:00 [pubmed]
PHST- 1999/01/26 00:01 [medline]
PHST- 1999/01/26 00:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 1999 Jan;5(1):119-27.