Comparison Of HER-2 Expression In Benign Prostate Hyperplasia With Prostate Cancer And The Analysis Of Correlation Of The HER-2 Expression Values And Gleason Scores By Using FQ-RT-PCR

Background and objective:Prostate cancer (PCa) and benign prostate hyperplasia (BPH) are two commom diseases for the elder men. In China 13.6% of the elder men suffered from BPH, and PCa accounts for approximately 13% of all cancer deaths. Prostate cancer is one of the common malignancy in genitourinary systemof man.In clinical, PSA is used for diagnosis of PCa, however, as a reslut of the insufficent specifity of PCa, elevated serum PSA levels may be the outcomes of prostatitis and BPH, even breast cancer. In particularly, it is diificult to distinguish PCa from BPH when serum PSA level is at 4-10 ng/ml. Affected by the subjective and empirical opinion of the pathologist, the Gleason score may be inaccurate. So searching more specific biomarkers for PCa and the pathology staging is pressing.The abnormal expression of HER—2/neu was found another key factor in the occurrence of cancer in rescent years' research.HER-2/neu has a low expression in many secretory epithelium normally.HER-2/neu takes a part in signal transmittion through many intracellular molecules.lt is basically thought that the overexpression of HER-2/neu can cause tumor through transactivating androgen receptor.In human cancers,the molecular alteration of HER-2/neu is generally the overexpression of normal gene outcome.Since the HER-2/neu protein locates in chorion and the diffussion is confined bidirectionally,even middle-level HER-2/neu overexpression could cause the activation.The HER-2/neu protein level of mamary cancer cell is 10-100 times higher than the adjacent normal epithelium through the immunohistochemical pigmentation.Craf.etc.castrated SCID male mice that had male-hormone-dependent type prostate cancer and got the male-hormone-independent prostate cancer derived from the originally male-hormone-dependent LAPC-4 type.HER-2/neu protein expression level enhanced 2-25 times.The overexpression of HER-2/neu has the function of promoting the male hormone independent-growth in vitro and in vivo.All these proved that the augmentation and overexpression of HER-2/neu is a very important factor that causes the protate cancer.In conclusion,the overexpression of HER-2/neu protein play a important role in the occurrence and development of prostate cancer,and might become a index to judge the outcome.Thus,the selection of HER-2/neu as the target gene in this research has sufficient lab base.HER-2/neu has very important physiological function which involves signal transfer intracellular,cell cycle regulatory,apoptosis and hermal creation in tumor etc..HER-2/neu-induced intracellular signal pathway includes mitogen-activated protein kinase(MAPK), phosphoinositide-3 kinase (PI-3K)/AKT pathway.MAPK is the main signal pathway for activating HER-2 and other tyrosine kinase.Another pathway induced by HER-2 is PI-3K/AKT pathway which plays a important role in the cell survival.HER-3 receptor could combine PI-3K motif,while HER-2 lack this.But HER-2 can induce HER-3 phosphorylation and then combines PI-3K,and the PI-3K/AKT kinase becomes activity.BAD and the caspase-9 were phosphorylated by the kinase as the targets.The phosphorylated AKT inhibits the glycogen synthesis kinase-Ⅲ, and the latter increases the cyclin D1 which starts the cell cycle.The transcript factor named Forkhead and Raf are also the direct/indirect targets of AKT.The last research work shows that over expression of HER-2/neu activate AKT and NF-κB which might resist the apoptosis and the cancer cells might be able to resistTNFaand might decrease the defense ability of the host to the tumor.Activated HER-2 can induce several separated pass ways activation,eg. PLC-γ/PI3-K,STAT/JAK,Ras/MAPK,stress activated protein kinase,Src,etc.and then the early gene-fos and jun were activated later.CyclinD and p27 might be the key factors which mediate the karyokinesis that induced by HER-2 and theGl/S transfer signal pass way.CyclinDl was up regulated by activated HER-2 through Ras/MAPK and PI3-K/AKT,then lowered the stability of p21,accelerated the transformation of G1/S and resisted apoptosis.While CyclinDl was down regulated,p27 was up regulated and Cdk2 was restricted by Herceptin which block the cell cycle.These results show that HER-2 might be a essential target for the tumor therapy.In this dissertation, we measured the value of HER2 gene expression in BPH and PCa tissue by using the way of FQ-RT-PCR.Comparing the pathology diagnosis and Gleason score with the value of hK2 gene, we try to illuminate the hK2 gene usage in the BPH and PCa. We hope to regonize the mechanism of hK2 gene in the level of molecular biology.Materials and methods:We collected the normal, BPH and PCa patients' prostatic tissue from September 2003 to December 2006.The HER-2 gene values were evaluated by using FQ-RT-PCR, the Gleason scores and pathology diagnosis were recorded as well. Comparion of the HER-2 gene value of BPH and Pca was made. And the dependability between the HER-2 gene value of BPH and PCa was calculated by statistics means.Statistical analysis:The comparion of measurement data sample mean in two group was accessed by t-test.The comparion of measurement data and ranked data was accessed by Spearman rank correlation analysis.Result:1. The HER-2 gene expression values between BPH and PCa are significantly different.2.The prostatic cancer HER-2 gene expression values variate in different Glseason score.The HER-2 gene expression values increase according to Gleason scores.Conclusion:1.The HER-2 gene expression values may be used to differentiate BPH and PCa.2. The HER-2 expression values is inversely correlated with Gleason scores. It increases with the increasing of Gleason scores.3. The HER-2 expression values my be used to evaluate the malignant degree of PCa.