PMID- 15556067
OWN - NLM
STAT- MEDLINE
DCOM- 20050512
LR  - 20211203
IS  - 1532-0456 (Print)
IS  - 1532-0456 (Linking)
VI  - 139
IP  - 1-3
DP  - 2004 Oct
TI  - IGF-binding proteins mediate TGF-beta 1-induced apoptosis in bovine mammary 
      epithelial BME-UV1 cells.
PG  - 65-75
AB  - TGF-beta 1 is an antiproliferative and apoptogenic factor for mammary epithelial 
      cells (MEC) acting in an auto/paracrine manner and thus considered an important 
      local regulator of mammary tissue involution. However, the apoptogenic signaling 
      pathway induced by this cytokine in bovine MEC remains obscure. The present study 
      was focused on identification of molecules involved in apoptogenic signaling of 
      transforming growth factor-beta 1 (TGF-beta 1) in the model of bovine mammary 
      epithelial cell line (BME-UV1). Laser scanning cytometry (LSC), Western blot and 
      electrophoretic mobility shift assay (EMSA) were used for analysis of expression 
      and activity of TGF-beta 1-related signaling molecules. The earliest response 
      occurring within 1-2 h after TGF-beta 1 administration was an induction and 
      activation of R-Smads (Smad2 and Smad3) and Co-Smad (Smad4). An evident formation 
      of Smad-DNA complexes began from 2nd hour after MEC exposure to TGF-beta 1. 
      Similarly to Smads, proteins of AP1 complex: phosphorylated c-Jun and JunD 
      appeared to be early reactive molecules; however, an increase in their expression 
      was detected only in cytosolic fraction. In the next step, an increase of IGF 
      binding protein-3 (IGFBP-3) and IGFBP-4 expression was observed from 6th hour 
      followed by a decrease in the activity of protein kinase B (PKB/Akt), which 
      occurred after 24 h of MEC exposure to TGF-beta 1. The decrease in PKB/Akt 
      activity coincided in time with the decline of phosphorylated Bad expression 
      (inactive form). Present study supported additional evidence that stimulation of 
      insulin-like growth factor I (IGF-I) was associated with complete abrogation of 
      TGF-beta 1-induced activation of Bad and Bax and in the consequence protection 
      against apoptosis. In conclusion, apoptotic effect of TGF-beta 1 in bovine MEC is 
      mediated by IGFBPs and occurs through IGF-I sequestration, resulting in 
      inhibition of PKB/Akt-dependent survival pathway.
FAU - Gajewska, Malgorzata
AU  - Gajewska M
AD  - Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw 
      Agricultural University, Nowoursynowska 159, 02-776 Warsaw, Poland.
FAU - Motyl, Tomasz
AU  - Motyl T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Comp Biochem Physiol C Toxicol Pharmacol
JT  - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
JID - 100959500
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Insulin-Like Growth Factor Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad4 Protein)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/physiology
MH  - Blotting, Western
MH  - Cattle
MH  - Cell Line
MH  - Cytosol/metabolism
MH  - DNA-Binding Proteins/drug effects/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Epithelial Cells/*drug effects/physiology
MH  - Female
MH  - Insulin-Like Growth Factor Binding Proteins/*metabolism
MH  - Mammary Glands, Animal/*drug effects/metabolism
MH  - Microscopy, Confocal
MH  - Protein Serine-Threonine Kinases/drug effects/metabolism
MH  - Proto-Oncogene Proteins/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-jun/drug effects/metabolism
MH  - Smad2 Protein
MH  - Smad3 Protein
MH  - Smad4 Protein
MH  - Time Factors
MH  - Trans-Activators/drug effects/metabolism
MH  - Transforming Growth Factor beta/*pharmacology/physiology
MH  - Transforming Growth Factor beta1
EDAT- 2004/11/24 09:00
MHDA- 2005/05/13 09:00
CRDT- 2004/11/24 09:00
PHST- 2004/07/15 00:00 [received]
PHST- 2004/09/07 00:00 [revised]
PHST- 2004/09/09 00:00 [accepted]
PHST- 2004/11/24 09:00 [pubmed]
PHST- 2005/05/13 09:00 [medline]
PHST- 2004/11/24 09:00 [entrez]
AID - S1532-0456(04)00175-9 [pii]
AID - 10.1016/j.cca.2004.09.006 [doi]
PST - ppublish
SO  - Comp Biochem Physiol C Toxicol Pharmacol. 2004 Oct;139(1-3):65-75. doi: 
      10.1016/j.cca.2004.09.006.