| The research on proteins related to centresomes debuts as another focus following cell cycle, information conduction and apoptosis. As well known, centresome is one of the cell organs with great importance during mitosis, and its normal replication plays a key role to maintain genome stability. Aurora-A, as a member found in recent years belonging to serine/threonine kinase family, proves relating to centresomes'maturation and chromosomes division. It has been confirmed as a new oncogene due to its high expression in multiple cancers cells, playing a key role in the normal process of mitosis as proved in previous researches. It may induce series of abnormalities resulting in oncogenesis, including the proliferation of centresomes, instability of chromosomes and the formation of aneuploid chromosomes. Based on series of researches, high expression of Aurora A mRNA and its protein have been observed in human malignancies from lots of organs, such as breast, stomach, liver, esophagus, bladder and pancreas, etc. Especially, the over expression and activation have been frequently detected in early ovary cancer or breast cancer. The inhibition on Aurora A can efficiently block tumors'growth and induce their apoptosis, which may be adopted as a new approach for many kinds of human cancers. In recent years, lung cancer has become a major concern from both oncologists and the public, with its increasing incidence and mortality worldwide. As one of the major malignancies in many countries, lung cancer is the first disease causing death with the highest incidence. Researchers worldwide has made a great deal of basic and clinical studies with many great development, in order to make clear the pathogenesis of lung cancer, decrease the incidence and mortality, then prevent the genesis and development of lung cancer. However, there is still a gap from complete controlling of and conquering on it. Up to now, the improved therapeutic results still depend on the key factors such as observation on early manifestation, early diagnosis and early treatment. Because advanced diseases has also been established in most cases of firstly-diagnosed lung cancer, it has become a focus to find a valuable tumor marker as well as an effective therapeutic target. Based on previous researches, reports on Aurora A in lung cancer are paradoxically scarce, even none in basic and clinical trials up to now, despite of concentrated focus on its functions in various cancers. In order to study its expression status in vivo and in vitro of lung cancer and its influence on genesis and development of lung cancer, following items were observed in this research. (1). Expression of its mRNA/ protein and DNA content in 3 lung cancer cell lines was observed through RT-PCR, Western Blot and CytoMeter, to study the relationship between expression status of Aurora A and the aneuploid chromosomes in vitro. (2). To study its expression status in vivo, levels of its mRNA and protein were observed in tumor samples from lung cancer patients through RT PCR, Western Blot and immunohistochemistry, with discussion on its clinical correlation. (3). CHO cells from a certain cell line is transfected with revised Aurora-A particles labeled with GFP, then the location of Aurora-A was observed with immunofluorescence as well as its influence on replication of centresomes, in order to discuss the possible mechanisms of its oncogenesis effect. As the results from semi-quantity RT-PCR on 3 lung cancer cell lines in this research, the aurora-A/β-actin ratio is 1.16, 1.14, 0.84 and 0.26, respectively in A549 (adeno-cancer), PG (highly metastatic giant cell cancer), NCI-H460 (large cell lung cancer) and normal lung tissue, implying higher expression of aurora-A mRNA in every cell line compared with normal lung tissue: with the highest in A549, middle in PG and lowest in NCI-460. Meanwhile, high expression of its protein was also observed through Western Blot in each cell line. Compared with diploid lung epithelial cells, positive belts of aurora-A appeared in all 3 kinds of lung... |
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