PMID- 16322332
OWN - NLM
STAT- MEDLINE
DCOM- 20060310
LR  - 20120604
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 12
IP  - 4
DP  - 2005 Dec
TI  - Activity and function of the nuclear factor kappaB pathway in human parathyroid 
      tumors.
PG  - 929-37
AB  - Previous studies indicate that nuclear factor kappaB (NF-kappaB) transcription 
      factor is deregulated and overexpressed in several human neoplasias. The aim of 
      this study was to test the hypothesis that the NF-kappaB pathway may be involved 
      in parathyroid tumorigenesis. For this purpose, we determined the level of 
      NF-kappaB activity, evaluated as phosphorylation of the transcription subunit 
      p65, its modulation by specific and non-specific agents and its impact on cyclin 
      D1 expression. Phosphorylated p65 levels present in parathyroid neoplasias (n = 
      13) were significantly lower than those found in normal tissues (n = 3; mean 
      optical density (OD) 0.19 +/- 0.1 vs 0.4 +/- 0.1, P = 0.007), but there was no 
      significant difference between adenomas and secondary and multiple endocrine 
      neoplasia type 1 (MEN1)-related hyperplasia. Conversely, MEN2A 
      (Cys634Arg)-related parathyroid samples showed extremely high levels of 
      phosphorylated p65 that exhibited a nuclear localization at immunohistochemistry 
      (n = 3). Phosphorylated p65 levels negatively correlated with menin expression 
      (r(2) = 0.42, P = 0.05). Tumor necrosis factor-alpha (TNFalpha) caused a 
      significant increase in phosphorylated p65 levels (183 +/- 13.8% of basal) while 
      calcium sensing receptor (CaR) agonists exerted a significant inhibition (19.2 
      +/- 3.3% of basal). Although TNFalpha was poorly effective in increasing cyclin 
      D1 expression, NF-kappaB blockade by the specific inhibitor BAY11-7082 reduced 
      FCS-stimulated cyclin D1 by about 60%. Finally, the inhibitory effects of CaR and 
      BAY11-7082 on cyclin D1 expression were not additive - by blocking NF-kappaB CaR 
      activation did not induce a further reduction in cyclin D1 levels. In conclusion, 
      the study demonstrated that in parathyroid tumors: (1) p65 phosphorylation was 
      dramatically increased by RET constitutive activation and was negatively 
      correlated with menin expression, (2) p65 phosphorylation was increased and 
      reduced by TNFalpha and CaR agonists respectively, and (3) blockade of the 
      NF-kappaB pathway caused a significant decrease in cyclin D1 expression.
FAU - Corbetta, S
AU  - Corbetta S
AD  - Institute of Endocrine Sciences, Fondazione Ospedale Maggiore IRCCS, University 
      of Milan, Italy.
FAU - Vicentini, L
AU  - Vicentini L
FAU - Ferrero, S
AU  - Ferrero S
FAU - Lania, A
AU  - Lania A
FAU - Mantovani, G
AU  - Mantovani G
FAU - Cordella, D
AU  - Cordella D
FAU - Beck-Peccoz, P
AU  - Beck-Peccoz P
FAU - Spada, A
AU  - Spada A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile)
RN  - 0 (MEN1 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitriles)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Sulfones)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
SB  - IM
MH  - Cyclin D1/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - NF-kappa B/analysis/antagonists & inhibitors/*metabolism
MH  - Nitriles/pharmacology
MH  - Parathyroid Glands/chemistry/metabolism/pathology
MH  - Parathyroid Neoplasms/chemistry/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins/analysis/metabolism
MH  - Proto-Oncogene Proteins c-ret/metabolism
MH  - Sulfones/pharmacology
MH  - Transcription Factor RelA/analysis/antagonists & inhibitors/*metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2005/12/03 09:00
MHDA- 2006/03/11 09:00
CRDT- 2005/12/03 09:00
PHST- 2005/12/03 09:00 [pubmed]
PHST- 2006/03/11 09:00 [medline]
PHST- 2005/12/03 09:00 [entrez]
AID - 12/4/929 [pii]
AID - 10.1677/erc.1.00970 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2005 Dec;12(4):929-37. doi: 10.1677/erc.1.00970.