Study on the Mutation of Kai-1/CD82 Gene in Colorectal Cancer ...

[Abstract]

Background: Invasion and metastasis is one of the importantcharacteristics of the malignant tumor and play a pivotal role in theprognosis of the tumor patients. In the recent years studies, invasion andmetastasis of the malignant tumor including many procedures is vividlyregarded as a process like the waterfall regulated by the oncogenes andtumor suppressor genes. A growing numerber of scholars suggest that theinactivation of the tumor suppressor genes is the main reason for themetastasis.Kai-1/CD82 was found recently as a metastasis suppression gene. Itbelongs to the transmemberane 4 superfamily in which members haveinhibitory effects on tumor cell motility and metastasis. It was reported thatKai-1/CD82 may have a significant role in the regulation of cell activation,migration, proliferation through modulation of cell-cell adhesion andcell-metrix adhesion. The abnormalities of the expression of Kai-1/CD82including the gene mutation, the loss of allic gene and change of the level ofexpression, were found in the process of metastasis of many tumors in thepast years study. Among these abnormalities, the relationship between thechange of the level of expression and the invasion and metastasis of tumorswas comfirmed in primary, but study on the relationship between themutation and loss of Kai-1/CD82 and the progression of tumors was stillcontroversial. In recent years, it was reported that the loss of exon 7 ofKai-1/CD82, found in the CT-26 cells in vivo (exon7 of the mice ishomologous with exon9 of human being), maybe contribute to theinactivation of this gene and attenuate its effect on the inhibitory of invasion and metastasis of tumors.Objective: The incidence rate increases gradually and now ranks thirdamong the gastroenterologic tumors in China. Further study on the mutationand loss of each gene in the process of the genesis and progression of theCRC would undoubtedly provide the theoretical evidence for the evaluationof prognosis and markers for the clinical therapy. This experiment is toexplore the significance mutation of the domain of exon 9 of Kai-1/CD82gene in the progression and metastasis of CRC.Methods: RNA was respectively extracted from 40 cases of the CRCtissues and 15 cases of the normal tissues near the CRC tissues. DNA wasextracted from the cases of the CRC tissues with the deletion of exon9 inKai-1/CD82 gene. The deletion of exon 9 was detected by using RT-PCRand validated by sequencing; The mutation of the domain of exon 9 ofKai-1/CD82 gene was detected by using PCR and judged by sequencing.Results: 1)The deletion in the Kai-1/CD82 gene was found in 18 of 40colorectal cases (45%) and in 2 of 15 normal cases near the CRCtissues(13.3%). The frequency of the deletion was significantly higher inthe CRC tumors than in the normal tissues near the CRC tissues. 2)Thefrequency of the deletion was significantly higher in the colorectal tumorswith lymphatic metastasis than that without lymphatic metastasis (P?0.05);3)in the advanced stage(Dukes C, D)than in the earlier stage(Dukes A, B) ofthe colorectal cancer (P?0.05); 4)there was no significant difference of thefrequency of the deletion when stratified by the the age, sex, histologicaltype as well as differentiated degree of the patients with CRC (P?0.05).Conclusion: The mutation of the domain of exon9 of the Kai-1/CD82gene was associated with the progression and metastasis of CRC and the detection of the mutation of the Kai-1/CD82 can be considered as aexperimental evidence for assessing the progression of colorectal cancer andguiding the clinical therapy.

Title: Study on the Mutation of Kai-1/CD82 Gene in Colorectal Cancer

Category: Cancer Cell

Filename: Study on the Mutation of Kai-1/CD82 Gene in Colorectal Cancer.pdf

Pages: 106

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