Cell-cycle regulator cyclin D1 mRNA 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 loss of tumor suppressor genes. The cyclin D1 gene encodes a proto-oncogenic cell cycle regulator implicated in the pathogenesis of several types of cancer, including gliomas. Northern blot analysis revealed expression of cyclin D1 mRNA in 7 (47%) of 15 primary glioma specimens. Immunohistochemistry using an antibody specific for cyclin D1 showed strong positivity amongst neoplastic glial cells in the same glioma samples. No cyclin D1 mRNA or protein was detected in 5 normal brain specimens. 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 overexpression of cyclin D1 mRNA and protein in primary human gliomas, and are consistent with a proposed oncogenic role of cyclin D1 in these tumors. It is suggested that excessive levels of cyclin D1 with or without several other D-type cyclin proteins may lead to deregulation of G(1) control in subsets of human gliomas. These results are further discussed in the context of putative functional redundancy of D-type cyclins and the role of the D-type cyclin/p16-ink4/pRB pathway in tumorigenesis.