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The Expression Of PI3K/PTEN/AKT Signal Pathway In Renal Cell Carcinoma And Their Clinical Significance

Posted on:2014-05-06Degree:MasterType:Thesis
Country:ChinaCandidate:L B ChenFull Text:PDF
GTID:2254330392473177Subject:Surgery
Abstract/Summary:PDF Full Text Request
Renal carcinoma is multigene tumour and its pathogenesis is considerably complicated.Molecular biology foundation of occurrence and development of disease course still can notbe clarified. Recently with further research in growth, proliferation, molecular mechanismapoptosis of tumour cell, it is discovered that imbalance in the body is one of the importantreason driving tumour progression, and disorder in the cell mainly leads to imbalance ofvarious signaling pathways in the cell. In the numerous signal transduction pathways inducedby tumour apoptosis, PI3K/PTEN/AKT signal transduction pathway is core of growthmodulation which plays an important role to adjust apoptosis. The activation of signaltransduction pathway can inhibit apoptosis induced by various stimulations and promoteprogress of cell cycles to facilitate cell survival and growth and angiogenesis, which hascritical role to play in the formulation of tumour, and participates invasion and metastasis oftumour. Meanwhile, this signal transduction pathway plays an important role in growth anddevelopment and drug resistant of malignant tumour by inducing cell occurrence and growthand angiogenesis.Currently, this pathway has drawn widespread attention due to therapeutictarget-centered oncotherapy. There are reports at home and abroad related to unusualactivation of PI3K/PTEN/AKT signaling pathway in leukemia and multiple myeloma andcancers such as lung, pancreas, liver, prostate, Kidney. However, the reports related torelationships between expression of PI3K protein, AKT protein and PTEN protein in renalcell carcinoma and growth and development of cell carcinoma in this signaling pathway arefewer. Mechanism of action of PI3K/PTEN/AKT signaling pathway in cell carcinoma is stillnot known now.ObjectiveThis research plans to examine expression changes of renal clear cell carcinoma and PI3K, PTEN, AKT in the adjacent tissues, analyzes correlation among PI3K, PTEN and AKT,relationships between PI3K, PTEN, AKT protein expression and clinical pathological featuresof renal cell carcinoma, and further discusses possible inter-relationship between PI3K/PTEN/AKT signaling pathway and renal clear cell carcinoma, and provides certain direction andtheory for new method to treat therapeutic target of renal cell carcinoma.Methods1.1The expression of PI3K protein, AKT protein and PTEN protein in renal clear cellcarcinoma and normal renal tissue is detected by immunohistochemical method.60cases ofrenal clear cell carcinoma and adjacent tissues are tissue specimens filed by pathologydepartment of Ningxia Medical University general hospital from2009to2011. Patients donot accept chemoradiotherapy and other antitumour therapies before operation.1.2The expression of PI3K, AKT and PTEN mRNA in renal clear cell carcinoma andnormal adjacent renal tissue are detected by reverse transcription polymerase chain reaction(RT-PCR) technology.40cases of renal clear cell carcinoma and adjacent tissues are tissuespecimens from urinary surgery of Ningxia Medical University general hospital from April2011to April2012. Patients do not accept chemoradiotherapy and other antitumor therapiesbefore operation. In addition,30cases of kidney tissues specimens from tumour verge>5cmare regarded as comparisons. Patients do not accept chemoradiotherapy and other antitumortherapies before operation. After separation all the tissues within five minutes must bequick-frozen in the liquid nitrogen and then reserved in the-80℃for detection.Results1.1Test results of immunohistochemical method: positive expression rate of PI3Kprotein and AKT protein in transparent renal cell carcinoma groups is obviously more thanadjacent tissues, and difference has statistically significant (P<0.05). Positive expression rate of PTEN protein in the transparent renal cell carcinoma tissues is obviously less than that ofadjacent tissues, difference has statistically significant (P<0.05). protein expression of PI3K,AKT and PTEN do not show obvious statistically differences in age and size of tumor, but interms of pathological grades and clinical stages, positive rate among groups has statisticallysignificant (P<0.05).1.2Test results of reverse transcription polymerase chain reaction (RT-PCR) technology:PI3KCA gene and AKT2gene in the renal clear cell carcinoma are high expression and lowexpression in the adjacent tissues, and difference has statistically significant (p<0.05). Theexpression of PTEN gene in the adjacent tissues is obviously more than that of renal clear cellcarcinoma, difference has statistically significant.Conclusion1. PI3K protein expression is high in the renal clear cell carcinoma tissues and low in theadjacent tissues. Expression of PI3K protein in the medium and slow differentiationcarcinoma tissues is more than high differentiation carcinoma tissues, which indicates thatPI3K protein may involve in occurrence and development of renal clear cell carcinoma.2. AKT protein expression in the renal clear cell carcinoma tissues is more than that ofadjacent tissues. AKT protein expression in the medium and slow differentiation carcinomatissues is more than that of high differentiation carcinoma tissues and indicates AKT proteinnot only involves in occurrence of renal clear cell carcinoma but also has critical role to playin pernicious development of renal clear cell carcinoma.3. PI3K protein and AKT protein in the renal clear cell carcinoma tissues are positivecorrelation, which indicates both are in the same signal transduction pathways and plays a roleto regulate occurrence and development of renal clear cell carcinoma.4.PTEN will lose with high proportion in renal clear cell carcinoma tissues and plays animportant role in occurrence and development of renal clear cell carcinoma. It is supposedthat PTEN can be regarded as prognostic factor of diagnosis, occurrence and development andprogress of renal clear cell carcinoma tissues.
Keywords/Search Tags:Renal cell carcinoma, PI3K, AKT, PTEN, Signal transduction pathwayconclusion
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