Expression And Significance Of Axin,β-catenin In Prostate Cancer

Background:Prostate cancer is one of the most common types of malignant tumor related to the urinary and male reproductive system diseases, and morbidity of prostate cancer is increasing year by year in China. The same as most of tumors, incidence of prostate cancer is complicated process with abnormality of multiple chromosomes, change of many genes and development of several procedures. Cellular signalling transduction is one of the most advanced and active topics in the current biomedical research field. It is well known that cellular activity is controlled by external signal and a series of reactions occur inside cells after external signal is transferred into cellular interior, and such process is called signalling transduction. Abnormal cellular signalling transduction will cause rapid proliferation and unlimited growing of cells, which is malignant tumor. Along with the development of molecular oncology and molecular pharmacology in recent years, functional mechanism of signalling transduction during tumor formation process is clarified step by step, and signalling transduction access has become new target of anti-tumor drugs. So the research on adjustment function and mechanism of tumor signalling transduction pathway is of important clinical meaning. Specific molecular research can offer theoretical basis for solving molecular biological characteristics of specific tumor and making individual therapy plan of tumor, and it can also further offer basis for research and therapy on clinical tumor gene. Wnt signalling transduction pathway is the known necessary signalling transduction pathway for embryonic development, and at the same time, it plays an important role in incidence and development of tumor. Excessive activation of such pathway plays an important role in incidence and development of prostate cancer. Wnt signalling transduction pathway is composed of Wnt protein, FZ protein, Dvl protein, APC composite (composed of glycogen synthesized urokinase, 3(GSK一3β), Axin protein and APC protein),β-catenin and transcription factors of Tcf/Lef. When there is mutation for Axin inside Wnt signalling, APC composite disintegrates and GSK-3βloses degradation activity onβ-catenin, to cause accumulation ofβ-catenin inside cells. When accumulatedβ-catenin reaches certain level inside cells, it will transfer to cell nucleus and form composite with transcription factors of Tcf/Lef, which will make cell cancerization through expression of target genes such as c-myc and cyclin D1. If Axin is normally expressed in Wnt signalling, composite will make phosphorylation ofβ-catenin andβ-catenin after phosphorylation will be further ubiquitnated and finally degraded to makeβ-catenin level keep at a low inside cytoplasm.Therefore Axin is an important negative adjustment molecular in Wnt/β-catenin signalling transduction pathway and its expression in low level can cause accumulation of freeβ-catenin inside cytoplasm. It is of great meaning to research on expression situations and mutual relationships between Axin andβ-catenin in prostate cancer tissues. There is much report on Axin andβ-catenin in aspects of esophageal cancer, hepatoma, and intestinal tumors in clinical trial, but little domestic and overseas reports on Axin andβ-catenin in Prostate cancer. Prostate cancer and prostatic hyperplasia tissue specimen was taken as a research objective in this research and fluorescent quantitation PCR and immunohistochemical methods used to test expression of Axin andβ-catenin inside to know about their expressing regulation in benign prostatic hyperplasia and prostate cancer and relationship with cancer pathology grading, which can offer certain experimental basis for further research on biological characteristics of prostate cancer.Purposes:It is to discuss expressing situations and differences of Axin andβ-catenin in benign prostatic hyperplasia and prostate cancer tissues, and relationship with cancer pathology grading, which can make certain experimental base for future introduction of Axin into prostate cancer molecular target therapy and explore Axin application in therapy of prostate cancer, especially of hormone refractory prostate cancer. (HRPC) Methods:Altogether 90 pieces of pathological specimen from benign prostatic hyperplasia and prostate cancer patients comply with experimental conditions from the urology of our hospital (with 45 cases of benign prostatic hyperplasia and 45 cases of prostate cancer), with No. for all specimens, which was respectively obtained and stored according to PCR and immunohistochemical detection. Fluorescent quantitation PCR method and immunohistochemical methods were adopted at the same time to test mRNA expression of Axin andβ-catenin in tumor and hyperplastic tissues. After datas collected, statistics method was adopted to analyze expression difference of two kinds of genes and proteins in cancer tissues and hyperplastic tissues, and relationship with cancer pathological grading.Results:Fluorescent quantitative PCR indicated that for all the 90 pieces of specimen (with 45 cases of benign prostatic hyperplasia and 45 cases of prostate cancer), expression for Axin gene mRNA in prostatic hyperplasia was obviously higher than that in prostate cancer tissues, with P < 0.05; while expression forβ-catenin gene mRNA in prostate cancer tissues was obviously higher than that in prostatic hyperplasia, with P < 0.05. For all 45 cases of prostate cancer patients, there was no obvious correlation between copy number of Axin mRNA and Geleason score of pathologic grading, however, there was obvious correlation between copy number ofβ-catenin mRNA and Geleason score of pathologic grading (r = 0.91).Immunohistochemistry results indicated that for all the 45 cases of prostate cancer specimen, positive staining ofβ-catenin protein occupied 83.3% (35/45) and for 45 cases of benign prostatic hyperplasia specimen, positive staining ofβ-catenin protein occupied 40% (18/45). Chi-sguare (X2) test was adopted, and there was statistics meaning for group differences (with P < 0.01). For prostate cancer tissues, positive staining of Axin protein occupied 28.9%(13/45)and for benign prostatic hyperplasia, positive staining of Axin protein occupied 80.0% (36/45), with obvious difference between groups for chi-sguare X2)) test (with P<0.01). After grouping all the prostate cancer patients according to ages and pathological grading after operation, it was found by analyzing expression relationship with Axin andβ-catenin protein that among the 45 patients, and among 22 cases with age > 70, 17 cases are positive expression ofβ-catenin protein, which reached 77.2%; and 23 cases with age < 70, 18 cases are positive expression ofβ-catenin protein, which reached 78.2%. It was found that P is more than 0.05 after adopting quadruple tabular form of chi-sguare(X2) test, without statistics meaning for the difference. The same theory was adopted to analyze Axin and it was found that there was no obvious statistics meaning for differences between Axin protein expression with ages of patients (with p > 0.05). Patients were grouped into high differentiation group and low to middle differentiation group (Gleason 2-4 as high differentiation group and Gleason 5-10 as low to middle differentiation group) according to pathological grading and it was found that after analyzing relationship between pathological grading.Theβ-catenin protein expression that there were 7 cases (53.4%) among 13 cases with positive expression ofβ-catenin in high differentiation group and there were 28 cases among 32 cases (87.5%) in low to middle differentiation group, indicating obvious difference betweenβ-catenin protein expression and pathological grading (with P < 0.05). The same theory was used to analyze Axin protein, and there was close relationship between its expression in cancer tissues and pathological grading (with P < 0.01). It was concluded that there was no obvious correlation between expression ofβ-catenin and Axin protein in prostate cancer tissues and age of patients, however, there was correlation between the expression and pathological grading of tumor. Positive expression ofβ-catenin protein for high differentiation group was obviously lower than that of low to middle differentiation group. For Axin, it was on the contrary, positive expression of Axin protein for low to middle differentiation group was obviously lower than that of high differentiation group.Conclusions:There was low mRNA expression of Axin and high expression ofβ-catenin in prostate cancer. There was positive correlation between copy number of mRNA ofβ-catenin and pathological grading of cancer, and positive expression ofβ-catenin protein in tumor tissues was obviously higher than that of benign prostatic hyperplasia, while positive expression of Axin protein in tumor tissues was obviously lower than that of benign prostatic hyperplasia. It further validated the possible relationship between the two during Wnt signalling transduction and offered experimental basis for introducing Axin to prostate cancer molecular target research. We found, at the same time, there was obvious correlation between expression ofβ-catenin and Axin protein in tumor tissues and pathological grading of tumor.