PMID- 8875753
OWN - NLM
STAT- MEDLINE
DCOM- 19970123
LR  - 20081121
IS  - 1050-7256 (Print)
IS  - 1050-7256 (Linking)
VI  - 6
IP  - 4
DP  - 1996 Aug
TI  - Alterations in TNF-alpha signal transduction in resistant human papillary thyroid 
      carcinoma cells.
PG  - 313-7
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) inhibit 
      the growth of the human papillary thyroid carcinoma (PTC) cell line, NP. Exposure 
      of NP cells to TNF-alpha resulted in the development of several PTC cell lines 
      (R30, R45, and R60) with graded loss to the TNF-alpha-induced antiproliferation, 
      termed resistance. In contrast, the NP cells and the resistant cells were equally 
      sensitive to the antiproliferative action of interferon-gamma. Utilizing 
      TNF-alpha receptor-specific agonist monoclonal antibodies, we demonstrated that 
      the TNF-alpha receptor p55 mediated the antiproliferative action of TNF-alpha, 
      while the p75 receptor did not affect cell proliferation in the NP cell line. The 
      resistant PTC cell lines, however, showed a graded loss of p55 receptor-mediated 
      antiproliferation and a concomitant activation of a p75 receptor-mediated growth 
      stimulation. Shedding of TNF receptors is an important mechanism of TNF-alpha 
      receptor metabolism. The p55 receptor mediated the TNF-alpha-induced 
      up-regulation of the shedding of the p75 TNF-alpha receptor. The p75 receptor 
      mediated the TNF-alpha-induced down-regulation of the shedding of the p55 
      receptor. However, the shedding of the p75 receptor was decreased and the 
      shedding of the p55 receptor was increased in the resistant R60 cell line 
      compared with the NP cell line, in the presence and absence of TNF-alpha. In 
      contrast, IFN-gamma increased shedding of both p55 and p75 TNF-alpha receptors in 
      NP and R60 cell lines with equal potency. Furthermore, the resistant PTC cell 
      lines have increased basal manganous superoxide dismutase (MnSOD) expression and 
      blunted induction of MnSOD mRNA upon short-term. TNF-alpha treatment (less than 2 
      h of treatment). The results indicate that a decrease in signal transduction via 
      the p55 TNF-alpha receptor and concomitant increase in signal transduction via 
      the p75 TNF-alpha receptor are involved in the development of PTC cell 
      resistance.
FAU - Pang, X P
AU  - Pang XP
AD  - Thyroid Cancer Research Laboratory, West Los Angeles VA Medical Center, 
      University of California 90073, USA.
FAU - Ross, N S
AU  - Ross NS
FAU - Hershman, J M
AU  - Hershman JM
LA  - eng
GR  - CA 61863/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Blotting, Northern
MH  - Carcinoma, Papillary/*physiopathology
MH  - Cell Division/drug effects
MH  - *Drug Resistance, Neoplasm
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Signal Transduction/*drug effects
MH  - Superoxide Dismutase/biosynthesis
MH  - Thyroid Neoplasms/*physiopathology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1996/08/01 00:00
MHDA- 1996/08/01 00:01
CRDT- 1996/08/01 00:00
PHST- 1996/08/01 00:00 [pubmed]
PHST- 1996/08/01 00:01 [medline]
PHST- 1996/08/01 00:00 [entrez]
AID - 10.1089/thy.1996.6.313 [doi]
PST - ppublish
SO  - Thyroid. 1996 Aug;6(4):313-7. doi: 10.1089/thy.1996.6.313.