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Relationship Between Proliferation/apoptosis Of Prostate Cancer And Androgen Receptor Expressing

Posted on:2005-02-05Degree:MasterType:Thesis
Country:ChinaCandidate:X W DiaoFull Text:PDF
GTID:2144360125465514Subject:Pathology
Abstract/Summary:PDF Full Text Request
Prostate cancer (PCa) is one of common malignant tumors in reproductive system of aged men. Decrease of Androgen level is close related with the carcinogenesis of prostate. Androgen activates Androgen Receptor (AR) to regulate development and secretion, maintains the balance of proliferation and apoptosis in prostate. Androgen level goes down with man old. It can cause secretion extraordinary of reproductive cell, and lead to out of balance of proliferation and apoptosis in prostate epithelium cell. This is one of most important causes of Prostate cancer developing. AR, as mark of Androgen depended cell, its mutation or deletion will alter peculiarity of AR distinguishing Androgen, effect active of itself, cause function of AR be inhibited or inactivated, various cell growth factors and Receptors express abnormal, activated of oncogenes or inactivated of tumor suppressor gene. There Regulative factors abnormal expressing are closely related with growth disorder of PCa, and make PCa cell flee proliferation suppressing from AR signal pathway, cause Androgen independed PCa occur, promote developing of PCa and failure of endocrine treatment at last.Proliferating cell nuclei antigen (PCNA) and Ki67 can specialized reflect Proliferative activity in cell cycle. Silver-stained nucleolar organizer regions (AgNORs) reflect growth speed and differentiated degree further by reflecting DNA ploids degree and function of ribosebody. Epidermal Growth Factor Receptor (EGFR) has activity of amino acid protease, it regulates cell growing and infiltrating by transducting cell Proliferation activated signal. AR expressing deletion may influence cell Proliferation effects by influencing expression of there related to proloiferative factors. BCL-2, reported in the literature as apoptosis suppressor gene, can regulate dynamic balance of cell apoptosis by combining Bax, as apoptosis gene, to form heterology biopolymer. Cell apoptosis occurring or not is determined upon expressing level and ratio of BCL-2 and Bax. Androgen and AR signal pathway take part in Regulating BCL-2 expressing level and activity. AR expressing deletion may influence cell apoptosis effects. Therefore we compare AR expressing normal and deletion in PCa with pathology purpose, to explore the relationships between AR and related to proliferate and apoptosis factors of PCa. It might help us to understand the mechanism of AR influencing Proliferation and apoptosis effects of PCa cell.Upon Relationship between AR and proliferation and apoptosis of PCa, our study collected 113 cases of PCa samples and 10 case of Benign prostate hyperplasia (BPH) samples (contrast), human PCa cell lines LNcap (Androgen depended PCa, AR expressing) and PC-3 (Androgen independed PCa, AR expressing deletion), to study Relationship between AR and proliferation/apoptosis of PCa with systematic by using the techniques immunohistochemistry, cell culture, RT-PCR, light/electron microscopy and image analysis. We would explore four questions as follow: (1) using immunohistochemistry technique labeling AR, study expressing characteristic of AR in three differentiated degrees of PCa, analyze difference of morphology between AR (+) groups and AR (-) groups of PCa, emphasis on exploring Relationship between AR expressing deletion and characteristic of pathology morphology; (2) using factors related to proliferation label PCNA, Ki67, AgNOR, EGFR, examine them expressing characteristic in AR(+)/AR(-) groups of PCa, explore Relationship between AR and proliferation of PCa; (3) using factors related to apoptosis label BCL-2, Bax, Tunel, examine there expressing characteristic in AR(+)/AR (-) groups of Pca, explore Relationship between AR and apoptosis of PCa; (4) by using different levels DHT stimulate cell lines LNcap and PC-3, examine EGFRmRNA and protein , Tunel expressing characteristic in different AR expressing of PCa, study Relationship between Androgen/AR and proliferation/apoptosis of PCa. Our studying tries to provide experimental basis to pathology and Clinical treatment of PCa.The main...
Keywords/Search Tags:Prostate cancer, Dihydrotestosterone (DHT), Androgen Receptor (AR), Proliferating cell nuclei antigen (PCNA), Ki67, AgNORs, Epidermal Growth Factor Receptor (EGFR), BCL-2, Bax, Terminal deoxy-transferase mediated x-Dutp end labeling (Tunel).
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