| Cyclins have a highly conserved motif called the 'cyclin box', which consists of a 100-amino acid motif which is conserved between all cyclins. Some cyclins associate with cyclin-dependent-kinases (CDK) via the cyclin box, and control cell cycle progression by functioning as the regulatory subunits of CDK that phosphorylate cellular substrates. Cyclin G1 was originally identified as a novel member of the cyclin family, than cyclin G2 was isolated as a homologue of cyclin G1. Cyclin I may also belong to the cyclin G subfamily because of its high sequence homology to cyclin G1 and cyclin G2. However, the precise functions of cyclin G1 and G2 remain unclear. Cyclin G1 is one of the target genes of the transcription factor p53. The cyclin G gene maybe involved in diverse cellular processes, including regulation of the cell cycle, apoptosis, DNA repair and cell differentiation.The physiological role and the expression of cyclin G1 is different in various organisation cells or in tumor cells from different sources. Some reports showed that the overexpression of cyclin G1 could promot the growth of tumor cells, and the antisense structure could inhibit cell growth. But others suggested that cyclin G1 probably had potential function of restraining cells growth and promoting apoptosis. In a word, the expresseion of cyclin G1 in mammalian cells has little effect on cell cycle progression, and only involve in the G2/M arrest and check point regulation in response to DNA damage and DNA restoration. But to some tumor cells, the meaning is different, cyclin G1 has function to promote the cell cycle progression, and relates with cell proliferation and differentiation. It suggest that the role of cyclinG1 in cell growth is not alike, and has tissue peculiarity, which also indicates the complexity of cyclin G1 gene, and is the entity of contradiction. Overexpression of the cyclin G1 (CYCG1) gene is frequently observed in some human tumor cells, and its continued expression is found to be essential for their survival. Previously, Skotzko et al. had reported that down-regulation of cyclin G1 protein expression induced cytostatic and cytocidal effects in human MG-63 osteosarcoma cells. Chen, et al. extend these findings in a tumorigenic MNNG/HOS cell line and reported on the effective inhibition of tumor growth in vivo by an antisense cyclin G1 retroviral vector when delivered as concentrated high titer vector supernatants directly into rapidly growing subcutaneous tumors in athymic nude mice. Histologic sections from the antisense cyclin G1 vector-treated tumors showed decreased mitotic indices and increased stroma formation within the residual tumors. Furthermore, Endo,et al. found that there were chromosomal translocations around the location of human cyclin G region which cause aberrant cyclin G expression in a manner that was causally related to leukemia. And aberrant cyclin G expression in human hematopoietic tumors have been reported, such as a subgroup of chronic myelomonocytic leukemia(CML), non-Hodgkin lymphoma(NHL), and acute lymphocytic leukemia(ALL). Classical cyclins promote cellular proliferation. They form complexes with specific CDK, thereby enabling CDK activation. Activated CDKs trigger cell cycle transitions through phosphorylation of specific targets such as the tumor suppressor Rb and cytoskeletal proteins. If the biology function of cyclins is disorder, it will certainly lead to unusual cell cycle and causes the unrestricted cell hyperplasia, which may contribute to tumorigenesis. In the advance experiment, we examined the expression of cyclin G1 mRNA by RT-PCR in HL60,K562 leukaemia cells and acute leukaemia(AL)patient ,and found that their expression is higher than normal control(NC), which indicated that cyclin G1 has some relation with leukaemia. Then we have performed series experiment:Part 1: Experimental study on the expression of Cyclin G1 in leukemic miceObjective: To study expression of cyclin G1,P53,P21,bcl-2 in leukemia mice,leukemic cells apoptosis... |
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