PATE,a gene expressed in prostate cancer, normal prostate, and testis, identified by a functional genomic approach
Tapan K. BeraRangan MaitraCarlo IavaroneGiuliana SalvatoreVasantha Kumar M.V.James J. VincentB. K. SathyanarayanaPaul H. DurayB. K. LeeIra Pastan
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To identify target antigens for prostate cancer therapy, we have combined computer-based screening of the human expressed sequence tag database and experimental expression analysis to identify genes that are expressed in normal prostate and prostate cancer but not in essential human tissues. Using this approach, we identified a gene that is expressed specifically in prostate cancer, normal prostate, and testis. The gene has a 1.5-kb transcript that encodes a protein of 14 kDa. We named this gene PATE (expressed in p rostate a nd te stis). In situ hybridization shows that PATE mRNA is expressed in the epithelial cells of prostate cancers and in normal prostate. Transfection of the PATE cDNA with a Myc epitope tag into NIH 3T3 cells and subsequent cell fractionation analysis shows that the PATE protein is localized in the membrane fraction of the cell. Analysis of the amino acid sequence of PATE shows that it has structural similarities to a group of proteins known as three-finger toxins, which includes the extracellular domain of the type β transforming growth factor receptor. Restricted expression of PATE makes it a potential candidate for the immunotherapy of prostate cancer.Early diagnosis and timely treatment are important for improving therapeutic efficiency of prostate cancer. DNA array is a new bio-technology for disease diagnosis. This study was conducted to diagnose prostate cancer with cDNA macroarray and analysis gene expression profiles of some selective genes in prostate cancer.Total RNA was isolated from patients with prostate cancer and from normal people, and poly (A) RNA was further purified. Then it was analyzed for differentially expressed genes in prostate cancer and normal prostate by cDNA macroarray system.There were different expressions in the nine prostate-associated specific genes in prostate cancer as compared with normal prostate, in which, 7 were significantly upregulated and 2 were down-regulated.As a diagnostic approach at molecular level, the cDNA macroarray is an effectively diagnostic method for prostate cancer.
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Prostate biopsy
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Objective: Study the level of 20 genes expression related with arsenic (sodium arsenite). Methods: First, 20 related genes were selected according to the mechanism of arsenism having reported and two control groups were set up. Then, the probs (23～30 mer) and arrays of oligonucleotide were made. Second, human hepatic cells (L 02) were cultured for two weeks exposing different arsenic concentrations, and total RNA was extracted, mRNA purificated, first strand cDNA synthesized, cDNA labelled using Cy\+5 and Cy\+3, cDNA broken using DNA enzyme, then cDNA and the probs hybridized and fluorescence signal scanned. Last, the values of Cy\+5: Cy\+3 were calculated to decide the level of those genes expression. Results: As compared with control, in 0.5 μM and 2.0 μM sodium arsenite groups, expression of C myc, ARS and CTF genes were inhibited, in 2.0 μM,expression of HGF gene was inhibited, but the expression of p53 gene was induced. Conclusion: Arsenic can inhibit the expression of CTF gene, starting of gene transcript was blocked, so it can cause the expression of many of genes to be declined. This result may be ones of the mechanisms of arsenical genetic toxicity.
Sodium arsenite
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Abstract Background Immunohistochemistry (IHC) to detect α‐methylacyl‐CoA racemase (AMACR) expression can be useful in the diagnosis of small foci of prostate cancer on needle biopsy specimens, although it still has limitations in terms of both sensitivity and specificity. We have previously described the increased expression of two prostate‐specific G‐protein coupled receptors (PSGR and PSGR2) in human prostate cancer. To examine their potential usefulness as cancer biomarkers, we have evaluated their expression relative to AMACR in prostate cancer tissues. Methods Expression of PSGR, PSGR2, and AMACR were examined by quantitative reverse‐transcriptase PCR in mRNAs from benign prostate and prostate cancer tissues. Expression of PSGR2 and AMACR was also examined by in situ hybridization using a prostate cancer tissue microarray. Results By in situ hybridization, 24 of 40 prostate cancer cases showed concordant expression of PSGR2 and AMACR. However, in 16 cases there was significant discordance between expression levels of these two markers. By quantitative RT‐PCR all three markers were substantially increased in cancer, with AMACR the most overexpressed (30‐fold), followed by PSGR2 (13‐fold) and PSGR (10‐fold). AMACR was the best single marker of prostate cancer but in 7 of the 59 total cases the expression of AMACR was not significantly elevated while PSGR and/or PSGR2 were substantially elevated. Conclusion All three biomarkers are increased in prostate cancer but their expression is not completely concordant. There is a subset of cases in which analysis of expression of PSGR and/or PSGR2, in addition to AMACR, would be diagnostically useful. Prostate © 2006 Wiley‐Liss, Inc.
Tissue microarray
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Objective To investigate the expressions of mitosis regulative factor STK-15 in prostate cancer and the relationship between STK-15 and the biological behavior of prostate cancer.Methods The expressions of STK-15 were examined by using immunohistochemical staining on 63 cases of prostate cancer and 16 cases of normal prostate tissues.And the expressions of STK-15 mRNA were detected by using RT-PCR in 14 cases of prostate cancer,BPH,and normal prostate tissues respectively.Results The STK15 protein was expressed in 98%(62/63) of prostate cancer tissue and in 19%(3/16) of normal prostate tissues.The difference between these expression rates was significant(P0.001).Meanwhile,the positive expression rates of STK-15 mRNA in prostate cancer,BPH,and normal prostate tissue were 93%(13/14),21%(3/14) and 14%(2/14) respectively.Compared with those in BPH and normal prostate tissue,the STK-15 mRNA expression rate in prostate cancer was significantly high(P0.001).Meanwhile,there was no significant difference between those in BPH and normal prostate tissue(P0.05).Conclusion The expressions of STK-15 increase in prostate cancer tissues which may contribute to the prostate carcinogenesis.
Prostate Diseases
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Study of Effect of Cydosporin A on Gene Differential Expression in Livers by cDNA Microarray in Rats
Objective To study the effects of cyclosporin A (CsA) on genes expression in rat liver. Methods The rats were sacrificed 24 hours after being orally treated once with cycolsporin A and the livers were taken out to extract total RNA. The cDNA derived from negative control group and CsA group livers were labded with Cy3 - dCTP and Cy5 - dCTP respectively. These probes were hybridized with cDNA microarray. The acquired image was scanned and analyzed by GenePix Pro 3.0 software. The intensity ratio of Cy5 to Cy3 about each spot was calculated. Results Among 4 096 genes, 50 genes exhibited differential expression in CsA group ,of which, 17 genes were up - regulated and 33 genes down - regulated. Conclusions The immuno - inhibitive effect, anti - cancer effects and interactions between CsA and other drugs may be related with the changes in the expressions of some associated genes.
Differential display
Gene chip analysis
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Objective To study the expression of kallikrein 7 (KLK7) in different prostate tissues and its clinical significance. Methods KLK7 mRNA levels in normal prostate epithelia (5 cases), benign prostat(ic) hyperplasia (BPH) epithelia (13 cases), prostate cancer and prostate cancer cell lines (8 cases) were analyzed by using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Western blot was used to analyze the protein levels of human kallikrein 7 (hK7) in benign prostate epithelia and prostate cancer cell lines, hK7 expressions were examined in 20 normal prostate tissue specimens, 50 BPH specimens and 103 prostate cancer specimens by immunohistochemical staining.Results The mRNA levels of KLK7 in normal prostate, BPH and prostate cancer were 0.59, 0.52 and 0.02 respectively, mRNA levels of KLK7 were significantly different among the three groups (F=13.03, P＜0.01). mRNA levels of KLK7 were decreased in prostate cancers compared with that in benign hyperplastic prostate epithelial cells (P＜0.01) and in normal prostate epithelial cells (P＜0.01). No significant difference of KLK7 mRNA levels was found between normal prostate and BPH. The protein levels of KLK7 in normal prostate, BPH, DU145, LNCaP, PC3,22RV1 and BPH1 was 0.22, O. 40, 0.01, 0.05, 0, 0.03 and 0.14 respectively, hK7 protein level was down-regulated in prostate cancer cell lines compared to benign prostate epithelial cells. The expression of bK7 was observed in benign prostate epithelial cells, whereas little or no staining was observed in prostate cancer cells in immunohistochemical study, hK7 protein was detected in 13 of 20 (65%)normal prostate specimens, 38 of 50 (76%) BPH specimens and 18 of 103 (17.5%) prostate cancer specimens. The difference between the normal prostate and prostate cancer was significant (Z=-4.43, P＜0.01). The difference between BPH and prostate cancer was significant (Z=-7.77,P＜0.01) as well. However, no significant difference of hK7 protein level was found between normal prostate and BPH (Z=-1. 52, P＞0.05). Conclusions KLK7 expression level is down regulated in prostate cancer. KLK7 may play an important role in prostate cancer progression.
Key words:
Prostatic neoplasms; Benign prostatic hyperplasia; Kallikrein
DU145
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Using the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute and American total mortality rates, the authors calculated the probability at birth of having a diagnosis of prostate cancer within a man's life to be 8.8% and then subtracted the incidence of microscopic Stage A cancers too small to ever be clinically significant. This gave a final probability of 8%.Prostates were examined after 139 consecutive unselected cystoprostatectomies from patients with bladder cancers in whom it was unknown whether they had prostate cancer. Prostate cancer was found in 55 patients (40%); the volume of the largest cancer in each specimen was determined using histologic morphometry. The authors identified the 8% of these 139 cytoprostatectomy specimens with the largest volume of prostate cancer.The largest 11 of the 55 cancers represented 7.9% of the total 139 samples. These cancers ranged in volume from 0.5-6.1 ml, representing only 20% of all patients with prostate cancer.If the strong evidence is accepted that cancer progression is proportional to cancer volume, it was concluded that prostate cancers larger than 0.5 ml appear to correspond to the 8% of men who will be diagnosed with a clinically significant carcinoma, as derived previously. Conversely, those 80% of prostate cancers smaller than 0.5 ml probably are not likely to reach a clinically significant size in view of the long doubling time of this cancer.
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