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.

Abstract

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.

• Authors: Juan-Carlos Martinez, Julio-Cesar Palomino, Rafael Samaniego, Juan M Sepulveda, Ana Cabello, Jose R Ricoy
• Journal: Cancer (Cancer) Vol. 113 Issue 1 Pg. 166-74 (Jul 01 2008) ISSN: 0008-543X [Print] United States
• PMID: 18459177 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (Copyright) 2008 American Cancer Society.

Chemical References

• Cyclin-Dependent Kinase Inhibitor p16
• Cyclins
• E2F1 Transcription Factor
• Retinoblastoma Protein
• Cyclin-Dependent Kinase 4

Topics

• Cyclin-Dependent Kinase 4 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p16 (metabolism)
• Cyclins (metabolism)
• E2F1 Transcription Factor (metabolism)
• Fluorescent Antibody Technique
• Humans
• Lasers
• Meningeal Neoplasms (metabolism)
• Meningioma (metabolism)
• Microscopy, Confocal
• Retinoblastoma Protein (metabolism)
• Signal Transduction