PMID- 18459177
OWN - NLM
STAT- MEDLINE
DCOM- 20080721
LR  - 20100324
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 113
IP  - 1
DP  - 2008 Jul 1
TI  - Retinoblastoma (Rb) tumor-suppressor pathway alterations in meningeal 
      hemangiopericytomas: High E2F transcription factor 1 expression and loss of Rb 
      expression: study by double immunofluorescence staining and laser-scanning 
      confocal microscopy.
PG  - 166-74
LID - 10.1002/cncr.23532 [doi]
AB  - BACKGROUND: The authors analyzed the retinoblastoma (Rb) tumor-suppressor pathway 
      in meningeal hemangiopericytomas (MHPCs). METHODS: : Immunohistochemical 
      detection of the Rb pathway proteins (Rb; E2F transcription factor 1 [E2F1]; 
      cyclins D1, D3, and E; cyclin-dependent kinase 4 [CDK4]; and the CDK4 inhibitor 
      p16/INKa) was followed by double immunofluorescence (DIF) staining and 
      laser-scanning confocal microscopy (LSCM) in 11 MHPC specimens and from 4 
      specimens of recurrent disease from 1, 2, and 4 recurrences (total, 18 
      specimens). RESULTS: : All specimens displayed Rb pathway alterations, including 
      low or negative Rb protein expression (17 specimens), high Rb protein expression 
      (1 specimen), and loss of p16/INK4a expression (17 specimens). High levels of 
      positive cell-cycle regulators were observed for E2F1 (10 specimens), cyclin E (7 
      specimens), CDK4 (5 specimens), cyclin D3 (1 specimen), and cyclin D1 (1 
      specimen). DIF and LSCM revealed no or very weak Rb and E2F1 colocalization, 
      indicating that Rb does not act as a growth suppressor. High levels of human 
      mouse double-minute 2 (HDM2) expression were observed in a previous study of 
      these tumors, and they displayed colocalization with E2F1 and Rb in the current 
      study, which supports the argument that HDM2 activates E2F1 and inactivates Rb. 
      CONCLUSIONS: : The current findings demonstrated that loss of Rb and p16/INKa 
      expression and high E2F1 expression indicate impairment of the Rb suppressor 
      pathway. HDM2 colocalization with E2F1 and Rb also indicates that Rb suppressor 
      pathway inactivation and transactivation of DNA synthesis genes may play 
      pathogenic roles in MHPCs. High expression levels of cyclin E, cyclin D1, cyclin 
      D3, and CDK4 were associated with Rb suppressor pathway neutralization.
CI  - (Copyright) 2008 American Cancer Society.
FAU - Martinez, Juan-Carlos
AU  - Martinez JC
AD  - Department of Pathology (Neuropathology), University Hospital 12th of October, 
      Madrid, Spain. jcmartinez.hrc@salud.madrid.org
FAU - Palomino, Julio-Cesar
AU  - Palomino JC
FAU - Samaniego, Rafael
AU  - Samaniego R
FAU - Sepulveda, Juan M
AU  - Sepulveda JM
FAU - Cabello, Ana
AU  - Cabello A
FAU - Ricoy, Jose R
AU  - Ricoy JR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Cyclins)
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (Retinoblastoma Protein)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
SB  - IM
MH  - Cyclin-Dependent Kinase 4/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p16/metabolism
MH  - Cyclins/metabolism
MH  - E2F1 Transcription Factor/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Lasers
MH  - Meningeal Neoplasms/*metabolism
MH  - Meningioma/*metabolism
MH  - Microscopy, Confocal
MH  - Retinoblastoma Protein/*metabolism
MH  - Signal Transduction
EDAT- 2008/05/07 09:00
MHDA- 2008/07/22 09:00
CRDT- 2008/05/07 09:00
PHST- 2008/05/07 09:00 [pubmed]
PHST- 2008/07/22 09:00 [medline]
PHST- 2008/05/07 09:00 [entrez]
AID - 10.1002/cncr.23532 [doi]
PST - ppublish
SO  - Cancer. 2008 Jul 1;113(1):166-74. doi: 10.1002/cncr.23532.