PMID- 10363999
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20200310
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 11
DP  - 1999 Jun 1
TI  - Increased smad expression and activation are associated with apoptosis in normal 
      and malignant prostate after castration.
PG  - 2731-8
AB  - Transforming growth factor (TGF)-beta1 is induced in the prostate after
      castration and has been implicated in apoptosis of epithelial cells during
      involution. TGF-beta1-mediated receptor activation induces phosphorylation of
      Smad2 and Smad3, which form complexes with Smad4, that translocate to the nucleus
      to regulate transcription of target genes. Smad6 and Smad7 antagonize the action 
      of signal-transducing Smads. We have examined the immunohistochemical expression 
      of different Smad molecules in the epithelium of rat ventral prostate before and 
      after castration, in androgen-sensitive Dunning R3327 PAP prostatic tumor cells
      from untreated and castrated rats, and after treatment with estrogen. In the
      ventral prostate, a significant increase of phosphorylated Smad2 (P-Smad2) was
      observed after castration. In prostatic tumor cells we observed an increased
      expression of Smad2 and P-Smad2 after treatment. The levels of Smad3 and, in
      particular, Smad4 were enhanced in the normal ventral prostate, as well as in the
      tumors after castration. Interestingly, Smad6 and Smad7 expression was also
      up-regulated in cells with increased Smad2 activation. The staining for Smad2,
      P-Smad2, Smad3, Smad4, and Smad7 was nuclear in some cells and was present in
      areas with a large number of apoptotic cells identified by various morphological 
      criteria, formation of apoptotic bodies and, in adjacent sections, by terminal
      deoxynucleotidyl transferase-mediated nick end labeling assay. Our results
      suggest that the signal transduction pathway for TGF-beta, leading to apoptosis, 
      is activated in the normal prostate after castration and in the tumor model after
      castration, without or with estrogen treatment.
FAU - Brodin, G
AU  - Brodin G
AD  - Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
FAU - ten Dijke, P
AU  - ten Dijke P
FAU - Funa, K
AU  - Funa K
FAU - Heldin, C H
AU  - Heldin CH
FAU - Landstrom, M
AU  - Landstrom M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, rat)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, rat)
RN  - 0 (Smad4 Protein)
RN  - 0 (Smad4 protein, rat)
RN  - 0 (Smad5 Protein)
RN  - 0 (Smad5 protein, rat)
RN  - 0 (Smad6 Protein)
RN  - 0 (Smad6 protein, rat)
RN  - 0 (Smad7 Protein)
RN  - 0 (Smad7 protein, rat)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - DNA-Binding Proteins/*metabolism
MH  - Male
MH  - Orchiectomy
MH  - Phosphoproteins/metabolism
MH  - Prostate/cytology/*metabolism
MH  - Prostatic Neoplasms/*metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Transforming Growth Factor beta/metabolism
MH  - Smad2 Protein
MH  - Smad3 Protein
MH  - Smad4 Protein
MH  - Smad5 Protein
MH  - Smad6 Protein
MH  - Smad7 Protein
MH  - Trans-Activators/*metabolism
MH  - Transforming Growth Factor beta/metabolism
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Jun 1;59(11):2731-8.