CELL-CYCLE REGULATOR CYCLIN D1 MESSENGER-RNA AND PROTEIN OVEREXPRESSION OCCURS IN PRIMARY MALIGNANT GLIOMAS

Gliomas are malignant brain tumors thought to arise through multi-step tumorigenesis, involving both the activation of oncogenes and the los s of tumor suppressor genes. The cyclin D1 gene encodes a proto-oncoge nic cell cycle regulator implicated in the pathogenesis of several typ es of cancer, including gliomas. Northern blot analysis revealed expre ssion of cyclin D1 mRNA in 7 (47%) of 15 primary glioma specimens. Imm unohistochemistry using an antibody specific for cyclin D1 showed stro ng positivity amongst neoplastic glial cells in the same glioma sample s. No cyclin D1 mRNA or protein was detected in 5 normal brain specime ns. Cyclin B, which has not been linked to tumorigenesis and serves as a marker for cellular proliferation, was expressed in all tumor, but not control, samples. These data provide the first evidence for the ov erexpression of cyclin D1 mRNA and protein in primary human gliomas, a nd are consistent with a proposed oncogenic role of cyclin D1 in these tumors. It is suggested that excessive levels of cyclin D1 with or wi thout several other D-type cyclin proteins may lead to deregulation of G(1) control in subsets of human gliomas. These results are further d iscussed in the context of putative functional redundancy of D-type cy clins and the role of the D-type cyclin/p16-ink4/pRB pathway in tumori genesis.