Intermediate filament expression in prostate cancer

Summary The human prostate is composed of a series of tubular-alveolar glands and their ducts surrounded by a fibromuscular stroma. The parenchymal glands secrete the seminal fluid and are anatomically arranged into the central, peripheral, and transitional zones. In this chapter the pattern of intermediate filament expression by the various epithelial components of the ducts, tubuloalveolar glands, and stroma are described. The changes which occur during malignant transformation from normal glands to prostatic intraepithelial neoplasia and subsequent invasive carcinoma are presented. The usefulness of cytokeratin markers in the diagnosis of prostate carcinoma is also discussed.     

MicroRNA expression profiling in prostate cancer

MicroRNAs (miRNA) are small, endogenously expressed noncoding RNAs that negatively regulate expression of protein-coding genes at the translational level. Accumulating evidence, such as aberrant expression of miRNAs, suggests that they are involved in the development of cancer. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature specific for prostate cancer, miRNA expression profiling of 6 prostate cancer cell lines, 9 prostate cancer xenografts samples, 4 benign prostatic hyperplasia (BPH), and 9 prostate carcinoma samples was carried out by using an oligonucleotide array hybridization method. Differential expression of 51 individual miRNAs between benign tumors and carcinoma tumors was detected, 37 of them showing down-regulation and 14 up-regulation in carcinoma samples, thus identifying those miRNAs that could be significant in prostate cancer development and/or growth. There was a significant trend (P=0.029) between the expression of miRNAs and miRNA locus copy number determined by array comparative genomic hybridization, indicating that genetic aberrations may target miRNAs. Hierarchical clustering of the tumor samples by their miRNA expression accurately separated the carcinomas from the BPH samples and also further classified the carcinoma tumors according to their androgen dependence (hormone naive versus hormone refractory), indicating the potential of miRNAs as a novel diagnostic and prognostic tool for prostate cancer.     

Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer

Pancreatic cancer is a devastating disease with poor prognosis. Production of large quantities of extracellular matrix and early metastasis are characteristics of this disease. One important step in the development of various cancers is the loss of E-cadherin gene expression or inactivation of E-cadherin mediated cell-cell adhesion. It has been shown that collagen type I promotes downregulation of E-cadherin expression, which correlates with enhanced cell migration and invasiveness. In this context, we elucidated the role of Smad-interacting protein 1 (SIP1), which has been discussed as a negative regulator of E-cadherin gene expression. We demonstrate that SIP1 upregulation shows an inverse relationship with E-cadherin in advanced pancreatic tumour stages. In Panc-1 cells, SIP1 expression can be induced by exposure to collagen type I in a src-dependent manner. In addition, overexpression of SIP1 reduces E-cadherin mRNA and protein levels. Taken together, these results suggest that SIP1 is involved in the progression of pancreatic cancer and plays a role in mediating signal transduction from collagen type I to downregulate E-cadherin expression.     

Stathmin基因表达与肿瘤的研究进展

Stathmin在多种恶性肿瘤细胞中都有高水平表达，Stathmin蛋白的主要作用是通过促进微管的解聚或阻止微管的聚合从而影响有丝分裂纺锤体的形成，通过抑制其表达可以干扰恶性肿瘤细胞的有丝分裂，影响肿瘤细胞的增殖与凋亡。同时，抑制stathmin表达能够协同增效某些化疗药物的抗癌疗效。Stathmin基因正成为肿瘤基因治疗的一个新靶点。     

Correlation of oncoprotein 18/stathmin expression in human breast cancer with established prognostic factors

Oncoprotein 18/stathmin (Op18) is a conserved cytosolic phosphoprotein that regulates microtubule dynamics. The microtubule destabilizing activity is regulated by phosphorylation, mediated by both growth factor stimulated- and cell-cycle regulating kinases. The protein is highly expressed in a variety of human malignancies. In human breast carcinoma, Op18 has previously been shown to be up-regulated in a subset of the tumours, however, no correlation with clinicopathologic characteristics has been reported so far. In the present study we have examined Op18 protein expression by quantitative Western blot analysis in a panel of 151 semi-consecutive breast carcinoma samples. Op18 levels were negatively correlated with oestrogen receptor (OR) expression and positively correlated with a high fraction of aneuploid cells, proliferation measured by proliferating cell nuclear antigen (PCNA) expression, tumour size and histopathologic grade. Taken together, and in contrast to what has been previously reported, the present study shows that high Op18 expression correlates with general predictive factors and is not restricted to a specific sub-group of breast carcinoma.     

血管内皮生长因子与前列腺癌的相关性研究

目的检测血管内皮生长因子(vascular endothelial growth factor,VEGF)在前列腺癌(human prostate cancer,PCa)和前列腺增生(benign of prostatic hyperplasia,BPH)中的表达,探讨VEGF与前列腺癌的相关性及其临床分期、病理分级的关系。方法收集整理我院1997至2004年收治的23例前列腺癌患者和10例前列腺增生患者的临床资料和病理蜡块标本,其中前列腺癌组为实验组,前列腺增生作对照组。采用原位杂交方法检测VEGF在前列腺癌和前列腺增生中的表达,用计算机图像分析系统分析其表达情况,并应用二步法免疫组化技术进一步验证其试验结果。结果VEGF在前列腺增生组织中呈低表达,前列腺癌组织中呈高表达。在前列腺癌组织的各临床分期和病理分级中,VEGF表达情况亦有差异性。结论VEGF与前列腺肿瘤的发病年龄、前列腺体积、血清前列腺特异抗原(prostatic special antigen,PSA)和组织类型无相关性;与前列腺增生亦无明显相关;与前列腺癌的生长、浸润和转移呈正相关,是检测前列腺癌的较好的分子标志物。     

Bax-interacting factor-1 expression in prostate cancer

BACKGROUND: Bax-interacting factor (Bif)-1 protein is a member of the endophilin B family that binds to and activates the proapoptotic Bax protein in response to apoptotic signals. Loss of Bif-1 suppresses the intrinsic pathway of apoptosis and promotes tumorigenesis. We examined the expression levels of Bif-1 protein in human prostate cancer. MATERIALS AND METHODS: Thirty-nine archival tissue specimens of human prostate cancer, and a human prostate cancer tissue microarray containing 19 samples of normal prostate, 26 samples of benign prostatic hyperplasias (BPHs), 30 samples of high-grade prostatic intraepithelial neoplasia (PIN), and 153 samples of prostate cancer, were selected for immunohistochemical staining with Bif-1 antibody. The slides were scored by 2 independent observers. RESULTS: Nontissue microarray samples: moderate to strong Bif-1 staining was identified in 38 of 39 prostate cancer samples. In 32 cases, foci of PIN were identified adjacent to prostate cancer samples. Of these, 29 samples (90.6%) showed strong and diffuse Bif-1 staining. Benign prostatic hyperplasias, identified in 27 cases, was weakly Bif-1 positive in 88.9% of cases. Tissue microarray samples: 38.6% (59 of 153) of prostate cancer samples showed moderate to strong Bif-1 expression, and 21.6% (33 of 153) were Bif-1 negative. Bif-1 expression was moderate to strong in 76.7% (23 of 30) of PIN. Bif-1 was weak to moderate in 53.8% (14 of 26) of BPH and negative in 46.2% (12 of 26) of them. Low to moderate Bif-1 was seen in 89.5% of normal prostate samples. CONCLUSION: The loss of Bif-1 expression in a subset of prostate cancer samples is in agreement with the proapoptotic function of Bif-1. The significance of the increased Bif-1 in a subgroup of prostate cancer samples and in PIN remains to be determined. It seems that Bif-1 has a role in prostate cancer, providing the rationale for using Bif-1 as a target for prostate anticancer therapy.     

人微管不稳定蛋白基因真核表达载体的构建与表达及对食管癌细胞的作用

目的 构建人微管不稳定蛋白基因(stathmin)真核表达载体,研究其对食管癌细胞EC9706的作用.方法 采用逆转录聚合酶链反应(RT-PCR)扩增stathmin cDNA,克隆至pMDl8-T载体并酶切鉴定后,亚克隆至pEGFP-C2真核表达载体.将测序鉴定正确的重组载体和空载体经脂质体转染EC9706细胞,G418筛选获得稳定转染的细胞株.通过荧光显微镜观察转染细胞荧光蛋白的表达,采用Western blot检测转染细胞中增强型荧光蛋白(EGFP)和stathmin融合蛋白的表达.选取稳定转染的细胞株,采用细胞计数法绘制细胞生长曲线,采用流式细胞仪分析细胞的增殖状态,平板克隆形成实验、裸鼠移植瘤实验分析转染细胞成瘤性.结果 RT-PCR扩增获得450 bp的cDNA编码序列;克隆至pMD18-T载体,经酶切鉴定后获反向插入质粒;亚克隆至pEGFP-C2载体后,经酶切与测序鉴定,重组载体pEGFP-stathmin构建成功.重组载体和空载体转染EC9706细胞,G418筛选获得稳定转染的细胞株.通过荧光显微镜观察到,转染细胞中呈现绿色荧光;经Western blot证实,重组载体表达46 000的融合蛋白.与空载体转染细胞相比,转染重组载体的EC9706细胞形态变大,增殖速度减慢,细胞分裂阻滞于G2/M期,细胞克隆形成数减少,裸鼠体内成瘤性降低(P＜0.05).结论 构建的真核表达载体pEGFP-stathmin在食管癌EC9706细胞中能够稳定表达,并抑制肿瘤细胞的增殖和成瘤性.     

Diagnostic performance of microRNAs expression in prostate cancer

MicroRNAs (miRNAs) have been proposed as ideal diagnostic indicators of prostate cancer (CaP). However, previous studies have reported conflicting results. Therefore, we conducted this meta-analysis to assess the potential diagnostic value of miRNAs for CaP. A systematic literature search was conducted in PubMed and other databases. Results from different studies were pooled using random effects models. The pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the overall test performance. Between-study heterogeneity was tested using the chi-squared test and the I ² test. Meta-regression and subgroup analyses were performed to explore the potential sources of heterogeneity. Fifty-eight studies from ten articles, including 669 patients with CaP and 404 controls composed of healthy individuals and patients with benign prostatic hyperplasia (BPH), were included in this meta-analysis. The pooled SEN and SPE were 0.74 (95 % confidence interval (CI) 0.70–0.78) and 0.73 (95 % CI 0.70–0.76), respectively. The pooled PLR was 2.7 (95 % CI 2.4–3.1); NLR was 0.35 (95 % CI 0.30–0.42); and DOR was 8 (95 % CI 6–10). The pooled AUC was 0.79 (95 % CI 0.76–0.83). Subgroup analyses indicated that multiple miRNAs yielded a better diagnostic accuracy. This systematic review suggests that miRNA analysis can significantly improve the overall accuracy of CaP diagnosis. Moreover, using multiple miRNA-based assays could achieve significantly higher accuracy in diagnosing CaP than single miRNA-based assays.