Heat shock protein 70 (HSP70) does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-beta1.
BACKGROUND
Mitogen-activated protein kinase (MAPK) is one of the transforming growth factor-beta (TGF-beta signaling pathways while heat shock protein 70 (HSP70) prevents apoptosis by affecting MAPK signaling downstream. However, the interrelationship between TGF-beta and HSP70 signaling is still unknown.


METHODS
DU-145 prostate cancer cells were treated with 40 pM and 200 pM TGF-beta1. After 3, 6, 9, 12 and 24 hours, cell proliferation assay and cell cycle analysis were performed. The activities of HSP70 and MAPKs (c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated kinase 1 (ERK1), ERK2 and p38) were analyzed by Western blot at each time-point.


RESULTS
TGF-beta1 inhibited the cell growth in a dose-dependent manner at 3 hours. Late G1 accumulation in the cell cycle was observed in a dose-dependent manner after 24 hours. HSP70 and JNK1 increased only at 3 hours and decreased for up to 24 hours thereafter. ERK1, ERK2 and p38 decreased from 3 to 24 hours after TGF-beta1 treatment.


CONCLUSIONS
These data suggest that HSP70 does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-beta1.
Ogawa
Y
Y
Department of Urology, Showa University School of Medicine, Tokyo, Japan. ogawayos@med.showa-u.ac.jp
Nakagami
Y
Y
Ishizaki
R
R
Yoshida
H
H
Parkinson
K M
KM
Robertson
C N
CN
Paulson
D F
DF
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D018840:HSP70 Heat-Shock Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020928:Mitogen-Activated Protein Kinases