PMID- 1572296
OWN - NLM
STAT- MEDLINE
DCOM- 19920603
LR  - 20071114
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 130
IP  - 5
DP  - 1992 May
TI  - Regulation of rat mammary epithelial cell proliferation and differentiation by 
      tumor necrosis factor-alpha.
PG  - 2833-44
AB  - The effect of tumor necrosis factor-alpha (TNF alpha) on the growth and 
      differentiation of normal rat mammary epithelial cells was evaluated using a 
      model system in which cells were grown within a reconstituted basement membrane 
      under defined serum-free medium conditions. TNF alpha (5-10,000 U/ml) stimulated 
      mammary epithelial cell proliferation both under conditions previously considered 
      optimal for their growth as well as in medium deficient in epidermal growth 
      factor (EGF). Moreover, TNF alpha could completely substitute for EGF for cell 
      proliferation. Under optimal conditions, TNF alpha had no effect on morphological 
      differentiation, but in medium either lacking or deficient in EGF or when 
      suboptimal reconstituted basement membrane was used, TNF alpha (5-100 U/ml) had a 
      marked stimulatory effect on lobular and ductal morphogenesis. The effect of TNF 
      alpha on functional differentiation, as assessed by casein production, was more 
      complex. In optimal lactogenic medium, TNF alpha (10-10,000 U/ml) inhibited 
      casein production. In the absence of EGF, however, the effect of TNF alpha 
      appeared to follow a bell-shaped curve. Thus, omission of EGF per se resulted in 
      a marked suppression of casein production, possibly secondary to an inhibition of 
      morphological development. At low concentrations (approximately 5 U/ml), TNF 
      alpha stimulated casein production in parallel to its stimulation of 
      morphological differentiation, although not to the same extent as in medium 
      containing optimal levels of EGF. However, once maximal stimulation of 
      morphogenesis had been achieved, further increasing the TNF alpha concentration 
      from 5 to 100 U/ml resulted in a concentration-dependent inhibition of casein 
      production. This suggests that TNF alpha may have a direct inhibitory effect on 
      casein gene expression. In summary, this is the first study to report that the 
      multifunctional cytokine TNF alpha is a potential regulator of the growth and 
      development of the mammary gland.
FAU - Ip, M M
AU  - Ip MM
AD  - Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263.
FAU - Shoemaker, S F
AU  - Shoemaker SF
FAU - Darcy, K M
AU  - Darcy KM
LA  - eng
GR  - CA-09072/CA/NCI NIH HHS/United States
GR  - CA-16056/CA/NCI NIH HHS/United States
GR  - CA-33240/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  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Caseins)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Animals
MH  - Basement Membrane/physiology
MH  - Caseins/analysis/metabolism
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Culture Media, Serum-Free
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epidermal Growth Factor/pharmacology
MH  - Epithelial Cells
MH  - Epithelium/drug effects/metabolism
MH  - Female
MH  - Kinetics
MH  - Mammary Glands, Animal/*cytology/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1992/05/01 00:00
MHDA- 1992/05/01 00:01
CRDT- 1992/05/01 00:00
PHST- 1992/05/01 00:00 [pubmed]
PHST- 1992/05/01 00:01 [medline]
PHST- 1992/05/01 00:00 [entrez]
AID - 10.1210/endo.130.5.1572296 [doi]
PST - ppublish
SO  - Endocrinology. 1992 May;130(5):2833-44. doi: 10.1210/endo.130.5.1572296.