Abstract A75: Retinoblastoma protein promotes Wnt signaling pathway activation in MC3T3 osteoblasts

Disruption of the retinoblastoma (pRb) pathway is observed in most cancers. Mutational inactivation of pRb itself is observed at high frequencies in retinoblastomas, osteosarcomas, and small cell lung carcinoma. pRb blocks cell cycle progression by repressing E2F‐dependent transcription of S‐phase‐related genes inducing cellular differentiation by serving as co‐activator of tissue‐specific transcription factors. Another pathway frequently targeted in human cancers is the Wnt pathway, which regulates a variety of processes such as chondrocyte and osteoblast differentiation. Wnt activation hinders β‐catenin degradation by proteosomes with consequent β‐catenin nuclear accumulation and transcription of Wnt target genes. In contrast, the absence of the Wnt signal allows the recruitment of CK1, APC, GSK3‐β, and β‐catenin by Axin. This complex phosphorylates β‐catenin at specific residues serving as a tag for recognition and degradation. Given that inactivation of both pRb and Wnt pathways is commonly observed in osteosarcomas, we sought to determine if these pathways are functionally linked in such a manner that inactivation of one of them leads to deregulation of the other. To test this, we performed qRT‐PCR of pRb‐expressing and pRb‐deficient osteoblasts (MC3T3 Rb +/+ and MC3T3 Rb −/− , respectively) in order to compare the mRNA steady state levels of the Wnt pathway components. We found a 1.8 fold increase (p Citation Information: Cancer Res 2009;69(23 Suppl):A75.