Elevated levels of cyclin D1 mRNA in the undifferentiated chick retina.

The retina is derived from precursor neuroectodermal cells that differentiate into six classes of neuronal cells and one class of glial cells (Müller). To gain insight into the molecular events underlying retinal differentiation, we used the differential display polymerase chain reaction (DD-PCR) technique to identify transcripts preferentially expressed in precursor retinal cells prior to their differentiation. One of the cDNAs that we selected using this technique encoded cyclin D1, a G1 cyclin shown to bind to the retinoblastoma protein (pRB) and which is involved in the phosphorylation of pRB during mid to late G1. Similar to what has been reported recently in the mouse retina, we found cyclin D1 mRNA to be highly expressed in the undifferentiated chick retina. Tissue maturation was accompanied by a substantial reduction in cyclin D1 mRNA levels. A similar temporal pattern of expression was observed in the developing brain although transcript levels were lower than in the retina. In contrast, cyclin D1 mRNA levels increased with differentiation in the kidney. These results suggest that the proliferating cells of the developing chick retina require exceptionally high levels of cyclin D1 mRNA, perhaps to promote progression through the cell cycle by countering the effect of molecules with a negative role in the cell cycle such as pRB.

Lack of expression of tumor-suppressor genes in human malignant glioma cell lines.

Human malignant gliomas (glioblastomas and anaplastic astrocytomas) are the most frequent brain tumors and are associated with a variety of genetic alterations including retinoblastoma (RB) and p53 gene mutations, loss of interferon alpha and beta (IFNA, IFNB) genes and lack of O6-methylguanine-DNA methyltransferase (MGMT) expression. Yet, in the studies performed to date, the relationship between these alterations has not been addressed. In this report, we have studied gene expression in 29 malignant glioma cell lines and have determined that, although loss of the interferon genes and loss of RB, p53 and MGMT mRNAs are frequent events, combinations of genetic alterations involving these four proven or putative tumor-suppressor genes are relatively infrequent. The exception was loss of RB mRNA, which may be associated with lack of MGMT mRNA.