Expression profiles and clinical relationships of ID2, CDKN1B, and CDKN2A inprimary neuroblastoma.
Journal Title: Genes, Chromosomes and Cancer - Year 2005, Vol 41, Issue 4
Abstract
Despite considerable research into the etiology of neuroblastoma, the molecularbasis of this disease has remained elusive. In contrast to the absence of expression of the known tumorsuppressor CDKN2A (also known as p16 and INK4A) in a wide variety of tumor types we have found in previousstudies that CDKN2A protein is paradoxically highly expressed in many advanced stage neuroblastomas andunrelated to RB1 status. In the present study, we sought to identify the mechanistic relationships thatmight influence CDKN2A expression and negate its influence on tumor cell proliferation. In this regard,we examined the role of the tumor-suppressor gene CDKN1B (also known as p27 and Kip1) and the oncogeneID2 in relationship to CDKN2A expression, MYCN amplification, and neuroblastoma pathogenesis in 17 neuroblastomacell lines and 129 samples of primary tumors of all stages. All neuroblastoma cell lines expressed theID2 transcript and protein. However, although the majority of primary neuroblastomas also expressed theID2 transcript, expression of the ID2 protein was undetectable or only barely detectable, regardlessof transcript expression. In both cell lines and primary tumors, ID2 expression was independent of bothCDKN2A and MYCN expression. In primary neuroblastomas, CDKN1B protein was expressed in significantlyfewer advanced-stage neuroblastomas than early-stage neuroblastomas, but its expression had no relationshipwith CDKN2A expression or MYCN amplification. We concluded that the paradoxical expression of CDKN2Ain neuroblastoma cannot be explained by inactivation of the tumor-suppressor gene CDKN1B or overexpressionof the oncogene ID2. We further concluded that ID2 is not a target of MYCN regulation nor is it a prognosticfactor for neuroblastoma. Finally, the loss of CDKN1B in advanced-stage neuroblastoma suggests this proteinmay play a role in the neuroblastoma disease process.
Authors and Affiliations
Sigrun Gebauer, Alice L Yu, Motoko Omura-Minamisawa, Ayse Batova, Mitchell B Diccianni
Keywords
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Expression profiles and clinical relationships of ID2, CDKN1B, and CDKN2A inprimary neuroblastoma.
Despite considerable research into the etiology of neuroblastoma, the molecularbasis of this disease has remained elusive. In contrast to the absence of expression of the known tumorsuppressor CDKN2A (also known as p16 a...