Retinoblastoma–Cyclin‐Dependent Kinase Pathway Deregulation in Vestibular Schwannomas

Abstract

The pRb-CDK pathway was altered in all vestibular schwannoma tumors examined, with CDK2 significantly downregulated in seven of the eight tumors. Further investigation into the regulatory mechanisms governing CDK2 expression may lead to a better understanding of vestibular schwannoma tumorigenesis.

The Molecular Biology of Vestibular Schwannomas and Its Association with Hearing Loss: A Review

“…The retinoblastoma protein (pRb) is encoded by the RB1 gene. Lasak et al [84] examined a deregulated signaling pathway, the retinoblastoma protein (pRb)-cyclin-dependent kinase (CDK) pathway, which was downregulated in 7 of 8 tumors. This signaling pathway is involved in the G1 to S cell cycle progression, promoting cell proliferation.…”

“…This signaling pathway is involved in the G1 to S cell cycle progression, promoting cell proliferation. As already stated by Cayé-Thomasen et al [23], the available data for the CDK pathway is conflicting, since one group found downregulation [84] while the other found upregulation [23]. Gonzalez-Gomez et al [22] had previously suggested an inverse link between the methylation of RB1 and p16 INK4a (found in 15% of samples) and cell cycle regulation, with the latter being altered through epigenetic changes.…”

Radiobiology of vestibular schwannomas: mechanisms of radioresistance and potential targets for therapeutic sensitization

“…Several studies have suggested an interaction between merlin and cell-cycle regulation via the pRb-CDK pathway. 13 Lasak and colleagues 17 have used microarray technology to study the G 1 to S phase cell-cycle pathway in VS tissue. Microarray chips with a large number of genes known to be important to the pRb-CDK pathway were generated and hybridized to cDNA from VS.…”

Cyclin D1 Expression and Histopathologic Features in Vestibular Schwannomas

“…Epigenetic changes have also been described in several genes, some of them with clinical implications on VS behavior (2). In addition to different mechanisms of gene inactivation, deregulated expression of growth regulatory genes may also play a role in the VS tumorigenesis (3). It has been shown that cyclin D1 is a key cell-cycle regulatory protein for the mammalian G1-S phase transition and is involved in the regulation of proliferation and differentiation.…”