Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased expression of JAG2, a target of miR-1280, is associated with high metastatic dissemination at diagnosis and a poor outcome in MB patients. Our study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as a key downstream effector of a PDGFRβ-driven signaling cascade and a potential therapeutic target.

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A cell line, designated BP6T, derived from Syrian hamster embryo (SHE) cells following treatment with benzo[a]pyrene is capable of producing tumors in newborn hamsters following the injection of as few as 1-10 cells. Polysomal poly(A) mRNA and total nuclear RNA obtained from this highly tumorigenic cell line were compared to RNAs obtained from the nonneoplastic parental embryo cells by a variety of techniques. RNA excess hybridizations to normal cell radiolabeled single-copy DNA or to a single-copy DNA tracer enriched for sequences transcribed in neoplastically transformed cells were unable to detect any significant differences in RNA sequence complexity between normal SHE cells and neoplastic BP6T cells. This finding of extensive homology of polysomal poly(A) mRNA and total nuclear RNA between normal and neoplastic cells, together with our previous finding of extensive homology of the major 35S-labeled nuclear or cytoplasmic polypeptides observable on two-dimensional gels [Leavitt, J. C., & Moyzis, R. K. (1978) J. Biol. Chem. 253, 2497-2500], demonstrates that the phenotypic changes associated with neoplastic transformation by chemical carcinogens are accompanied by relatively few changes in the qualitative pattern of gene expression in cells cultured in vitro.