Cyclin D1/PRAD1/BCL-1 alternative transcript [B] protein product in B-lymphoid malignancies with t(11;14)(q13;q32) translocation

Abstract

The cyclin-D1/PRAD1 oncogene, a key regulator of the G1-phase progression of the cell cycle, has been identified as the long-sought BCL-1 oncogene in B-cell malignancies with t(11;14)(q13;q32) translocation. A novel alternative spliced cyclin-D1 transcript, called transcript[b], has been identified. The level of the variant transcript[b] was lower than that of the originally reported cyclin-D1 transcript, called transcript[a], in several human non-lymphoid cancer cell lines but the endogenous cellular expression of transcript[b] products has not yet been determined. Northern-blot analysis and reverse-transcription-polymerase-chain-reaction (RT-PCR) analysis revealed that transcript[b] mRNA is well expressed in B-lymphoid cell lines with t(11;14)(q13;q32) translocation and at much lower or undetectable levels in other cells. Western-blot analysis using a human cyclin-D1-specific monoclonal antibody, which can recognize and distinguish the products of transcripts [a] and [b], strongly suggested that the transcript [b] protein is indeed expressed in these B-cell lines. The present study provides identification of the endogenous cellular expression of the cyclin-D1-transcript[b] protein and strongly suggests that this alternative form of cyclin D1 may play a significant role in the molecular pathogenesis of B-lymphoid malignancies with t(11;14)(q13;q32) translocation.