PMID- 9275079
OWN - NLM
STAT- MEDLINE
DCOM- 19970918
LR  - 20181130
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 138
IP  - 9
DP  - 1997 Sep
TI  - The epidermal growth factor receptor is not required for tumor necrosis 
      factor-alpha action in normal mammary epithelial cells.
PG  - 3891-900
AB  - Our laboratory has shown that tumor necrosis factor-alpha (TNF alpha) can 
      regulate normal mammary epithelial cell (MEC) growth, morphogenesis, and, under 
      certain circumstances, functional differentiation in a manner similar to 
      epidermal growth factor (EGF). As TNF alpha has been shown to up-regulate EGF 
      receptor (EGFR) expression and function in other systems, the present studies 
      were undertaken to determine whether TNF alpha action in MEC was indirect through 
      stimulation of the EGFR. An inhibitor of EGFR tyrosine kinase activity, PD158780, 
      failed to block proliferation induced by 40 ng/ml TNF alpha and only partially 
      inhibited growth in response to 2 ng/ml TNF alpha. PD158780 was also unable to 
      suppress the extensive morphological development induced by either TNF alpha 
      concentration. In contrast, the effects of TNF alpha and PD158780 on functional 
      differentiation (i.e. casein accumulation) were time dependent. When measured on 
      day 7 after 48 h of treatment, casein accumulation was unaffected by either 
      concentration of TNF alpha or by PD158780. When assessed on day 21 after 16 days 
      of treatment, however, casein levels were decreased by 40 ng/ml TNF alpha and 
      increased by PD158780. Significantly, this PD158780-induced increase in casein 
      was not observed in MEC that had been treated with both PD158780 and TNF alpha. 
      These results thus suggest that EGFR tyrosine kinase activity is not necessary 
      for TNF alpha action in normal MEC.
FAU - Varela, L M
AU  - Varela LM
AD  - Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263, 
      USA.
FAU - Darcy, K M
AU  - Darcy KM
FAU - Ip, M M
AU  - Ip MM
LA  - eng
GR  - CA-09072/CA/NCI NIH HHS/United States
GR  - CA-16056/CA/NCI NIH HHS/United States
GR  - CA-57317/CA/NCI NIH HHS/United States
PT  - Journal Article
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  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (6-(methylamino)pyrido(3,4-d)pyrimidine)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells
MH  - ErbB Receptors/antagonists & inhibitors/*physiology
MH  - Female
MH  - Mammary Glands, Animal/*cytology
MH  - Pyrimidines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1997/09/01 00:00
MHDA- 1997/09/01 00:01
CRDT- 1997/09/01 00:00
PHST- 1997/09/01 00:00 [pubmed]
PHST- 1997/09/01 00:01 [medline]
PHST- 1997/09/01 00:00 [entrez]
AID - 10.1210/endo.138.9.5389 [doi]
PST - ppublish
SO  - Endocrinology. 1997 Sep;138(9):3891-900. doi: 10.1210/endo.138.9.5389.