PMID- 15647840
OWN - NLM
STAT- MEDLINE
DCOM- 20050808
LR  - 20131121
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 15
IP  - 2
DP  - 2005 Feb
TI  - Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and 
      repression of E2F in androgen-treated LNCaP human prostate cancer cells.
PG  - 253-8
AB  - Bone morphogenetic protein-2 (BMP-2), a multifunctional member of the 
      transforming growth factor (TGF)-beta, superfamily, has powerful osteoinductive 
      effects and causes cell cycle arrest in a variety of transformed cell lines. We 
      have observed BMP-2-induced inhibition of cell proliferation in an 
      androgen-dependent human prostate cancer cell line (LNCaP). To investigate the 
      mechanism of inhibition of androgen-dependent growth by BMP-2, we examined the 
      effect of dihydrotestosterone (DHT) and/or BMP-2 on cell cycle-related proteins 
      in LNCaP cells. BMP-2 decreased the phosphorylation of retinoblastoma (Rb) 
      protein induced by treatment with DHT. DHT-induced expression of cyclin A and 
      cyclin-dependent kinase 2 (CDK2) protein was also inhibited by co-treatment with 
      BMP-2. Furthermore, BMP-2 induced expression of p21(WAF1/CIP1), a CDK inhibitor. 
      These results indicate that changes in expression of these proteins lead to 
      modulation of the phosphorylation state of Rb. DHT-induced E2F-1 protein and mRNA 
      expressions was also inhibited by BMP-2, suggesting that BMP-2 inhibits 
      DHT-induced growth of LNCaP cells through a decrease in E2F protein expression 
      and suppression of E2F activity by hypophosphorylation of Rb.
FAU - Tomari, Kentaro
AU  - Tomari K
AD  - Department of Hygiene-chemistry, Faculty of Pharmaceutical Sciences, Tokyo 
      University of Science, Chiba 278-8510, Japan.
FAU - Kumagai, Toru
AU  - Kumagai T
FAU - Shimizu, Takahisa
AU  - Shimizu T
FAU - Takeda, Ken
AU  - Takeda K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Androgens)
RN  - 0 (BMP2 protein, human)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin A)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F Transcription Factors)
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (E2F1 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 63231-63-0 (RNA)
RN  - J4Z741D6O5 (Gentian Violet)
SB  - IM
MH  - Androgens/*metabolism/*pharmacology
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Bone Morphogenetic Protein 2
MH  - Bone Morphogenetic Proteins/metabolism/*physiology
MH  - Cell Cycle
MH  - Cell Cycle Proteins/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cyclin A/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - DNA-Binding Proteins/*metabolism
MH  - Dihydrotestosterone/pharmacology
MH  - E2F Transcription Factors
MH  - E2F1 Transcription Factor
MH  - *Gene Expression Regulation, Neoplastic
MH  - Gentian Violet/pharmacology
MH  - Humans
MH  - Male
MH  - Phosphorylation
MH  - Prostatic Neoplasms/*metabolism
MH  - RNA/metabolism
MH  - RNA, Messenger/metabolism
MH  - Retinoblastoma Protein/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Transcription Factors/*metabolism
MH  - Transforming Growth Factor beta/metabolism/*physiology
MH  - Up-Regulation
EDAT- 2005/01/14 09:00
MHDA- 2005/08/09 09:00
CRDT- 2005/01/14 09:00
PHST- 2005/01/14 09:00 [pubmed]
PHST- 2005/08/09 09:00 [medline]
PHST- 2005/01/14 09:00 [entrez]
PST - ppublish
SO  - Int J Mol Med. 2005 Feb;15(2):253-8.