Abstract
Cyclin D1 plays a key regulatory role during the G1 phase of the cell cycle and its gene is amplified and over-expressed in many cancers. The cyclin D1b mRNA variant was established in human cells and recent functional analyses revealed that its protein product harbors unique activities in human cancer cells. By performing reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) experiments, we identified the cyclin D1b mRNA variant in mouse. Similar to its human counterpart, the mouse cyclin D1b transcript consists of exon 1, 2, 3, 4 and part of intron 4, and contains a long open reading frame (ORF). The predicted peptide from this ORF is 34-amino acid longer than the human cyclin D1b. The expression of this mouse mRNA variant was investigated. It appears to be expressed ubiquitously and differentially in various mouse cell lines and tissues and its level might be proportional to that of the canonical endogenous cyclin D1a mRNA.
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References
Sherr CJ (1995) D-type cyclins. Trends Biochem Sci 20:187–190
Sherr CJ (2000) The Pezcoller lecture: cancer cell cycles revisited. Cancer Res 60:3689–3695
Peters G (1994) The D-type cyclins and their role in tumorigenesis. J Cell Sci Suppl 18:89–96
Arnold A (1995) The cyclin D1/PRAD1 oncogene in human neoplasia. J Invest Med 43:543–549
Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677
Palmero I, Peters G (1996) Perturbation of cell cycle regulators in human cancer. Cancer Surv 27:351–367
Diehl JA (2002) Cycling to cancer with cyclin D1. Cancer Biol Ther 1:226–231
Betticher DC, Thatcher N, Altermatt HJ, Hoban P, Ryder WD, Heighway J (1995) Alternate splicing produces a novel cyclin D1 transcript. Oncogene 11:1005–1011
Solomon DA, Wang Y, Fox SR, Lambeck TC, Giesting S, Lan Z, Senderowicz AM, Conti CJ, Knudsen ES (2003) Cyclin D1 splice variants. Differential effects on localization, RB phosphorylation, and cellular transformation. J Biol Chem 278:30339–30347
Lu F, Gladden AB, Diehl JA (2003) An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res 63:7056–7061
Burd CJ, Petre CE, Morey LM, Wang Y, Revelo MP, Haiman CA, Lu S, Fenoglio-Preiser CM, Li J, Knudsen ES, Wong J, Knudsen KE (2006) Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation. Proc Natl Acad Sci USA 103:2190–2195
Knudsen KE (2006) The cyclin D1b splice variant: an old oncogene learns new tricks. Cell Div 24:1–15
Biliran H Jr, Wang Y, Banerjee S, Xu H, Heng H, Thakur A, Bollig A, Sarkar FH, Liao JD (2005) Over-expression of cyclin D1 promotes tumor cell growth and confers resistance to cisplatin-mediated apoptosis in an elastase-myc transgene-expressing pancreatic tumor cell line. Clin Cancer Res 11:6075–6086
Wang Y, Thakur A, Sun Y, Wu J, Biliran H, Bollig A, Liao DJ (2007) Synergistic effect of cyclin D1 and c-Myc leads to more aggressive and invasive mammary tumors in severe combined immunodeficient mice. Cancer Res 67:3698–3707
Aslakson CJ, Miller FR (1992) Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res 52:1399–1405
Biliran H Jr, Banerjee S, Thakur A, Sarkar FH, Bollig A, Ahmed F, Wu J, Sun Y, Liao JD (2007) c-Myc-induced chemosensitization is mediated by suppression of cyclin D1 expression and nuclear factor-kappa B activity in pancreatic cancer cells. Clin Cancer Res 13:2811–2821
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
Sanchez G, Bittencourt D, Laud K, Barbier J, Delattre O, Auboeuf D, Dutertre M (2008) Alteration of cyclin D1 transcript elongation by a mutated transcription factor up-regulates the oncogenic D1b splice isoform in cancer. Proc Natl Acad Sci USA [Epub ahead of print]
Howe D, Lynas C (2001) The cyclin D1 alternative transcript [a] and [b] are expressed in normal and malignant lymphocytes and their relative levels are influenced by the polymorphism at codon 241. Haematologica 86:563–569
Carrère N, Belaud-Rotureau MA, Dubus P, Parrens M, de Mascarel A, Merlio JP (2005) The relative levels of cyclin D1a and D1b alternative transcripts in mantle cell lymphoma may depend more on sample origin than on CCND1 polymorphism. Haemotologica 90:854–856
Zwicker J, Brüsselbach S, Jooss KU, Sewing A, Behn M, Lucibello FC, Müller R (1999) Functional domains in cyclin D1: pRb-kinase activity is not essential for transformation. Oncogene 18:19–25
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This work was supported by NIH grant R01CA100864 (J.D.Liao).
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Wu, J., Wu, Sh., Bollig, A. et al. Identification of the cyclin D1b mRNA variant in mouse. Mol Biol Rep 36, 953–957 (2009). https://doi.org/10.1007/s11033-008-9267-7
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DOI: https://doi.org/10.1007/s11033-008-9267-7