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The Expression And Clinical Significance Of The Family Of Apoptosis Stimulating Protein Of P53 In Gastric Cancer

Posted on:2012-01-18Degree:MasterType:Thesis
Country:ChinaCandidate:H Y LiangFull Text:PDF
GTID:2214330368992521Subject:Oncology
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Objective To approach the expression of ASPP family(including ASPP1, ASPP2 and iASPP)in human gastric cancer tissues, and to explore the association between the mRNA expression of ASPP family genes and clinicopathological features in gastric cancer. The association between the ASPP mRNA and the chemosensitivity to chemotherapy drugs cisplatin and the influence of chemotherapy drugs on the expression of the ASPP family in gastric cancer cells was also investigated.Methods The expression of ASPP family mRNA was detected in 60 cases gastric cancer tissue and paracarcinomatous tissue by reverse transcription-polymerase chain reaction (RT-PCR) , reviewed the clinical data and studied the clinicopathological implications of these cases. Gastric cancer cell lines AGS (wild-type p53) and SGC-7901 (mutant-type p53) with different p53 genetic background were treated with DDP(cisplatin), and chemosensitivity of the cell lines to DDP was analyzed by MTT assay, RT-PCR was also used to measure the mRNA levels of ASPP family around the treatment.Results 1. The iASPP mRNA expression in gastric cancer and para-cancerous tissues were 85.0% (51/60) and 18.3% (11/60) respectively, and the levels of the iASPP expression in gastric cancer and para-cancerous tissues were 0.503±0.336 and 0.205±0.108 respectively. The expression of iASPP in gastric cancer tissues was significantly higher than in paracarcinoma tissues(P<0.05). Overexpression of iASPP was related to tumor differentiation degree and invasion depth(P<0.05), but not to gender, age, tumor size, lymphatic metastasis and clinical staging.2. The MTT results implicate that the inhibition ratio of SGC-7901 cell line to was3.6μg/ml, while AGS cell line was 10.5μg/ml.3. ASPP1,ASPP2 and iASPP mRNA expression in AGS cell line and SGC-7901 cell line was found different, the mRNA expression index (RI) of ASPP1, ASPP2 and iASPP in AGS cell line were 0.139±0.003,0.527±0.062,0.566±0.023, while in SGC-7901 cell line were 0.343±0.024,0.708±0.017,0.485±0.023, ASPP1 and ASPP2 mRNA expression in AGS cell linewas lower than in SGC-7901 cells, however, the iASPP mRNA expression was higher in AGS cells than in SGC-7901 cells(P<0.05). After 24h treatment with DDP, the ASPP1 mRNA expression index was 0.151±0.007,with no difference compared to no treatment(P>0.05), the ASPP2 mRNA expression index was 0.746±0.059,significantly higher than before treatment(P<0.05),the iASPP mRNA expression was 0.574±0.039,with no difference to no treatmentwhile(P>0.05). the RI of ASPP1, ASPP2 in SGC-7901 cell line were 0.414±0.020,0.790±0.021,significantly higher than before treatment(P<0.05),the iASPP RI was 0.426±0.012,lower than before treatment(P<0.05).Conclusion Overexpression of iASPP was related to tumor differentiation degree and invasion depth in gastric cancer. Cisplatin can induce up-regulation of ASPP2 mRNA in AGS human gastric cancer cells with p53-wild type, induce up-regulation of ASPP1,ASPP2 mRNA but down-regulation of iASPP in SGC-7901 human gastric cancer cells with p53-mutant type. SGC-7901 human gastric cancer cells with p53- mutant type has high chemosensitivity to cisplatin than AGS human gastric cancer cells with p53-wild type, maybe because SGC-7901 cells has a higher expression of ASPP1 and ASPP2 mRNA and lower expression of iASPP mRNA basically and after induction than AGS cells.
Keywords/Search Tags:The ASPP family, Gastric cancer, Cisplatin, RT-PCR
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