胰岛素样生物因子Ⅰ,Ⅱ与其受体mRNA在前列腺增生组织中表达

采用地高辛标记的ｃＲＮＡ探针行细胞原位杂交技术，对良性前列腺增生（ＢＰＨ）组织中胰岛素样生长因了及受体的基因表达情况进行了研究，结果显示：１４／１６例ＢＰＨ组织中ＩＧＦ－ⅠｍＲＮ阳性表达，定位在上皮和基质组织；１１／１２例ＢＰＨ组织中，ＩＧＦ－ⅡｍＲＮＡ阳性表达，定位基质；ＩＧＦ－Ⅰ受体ｍＲＮＡ在所检测的８例标本中均在表达，主要定位于上皮，而ＩＧＦ－Ⅱ受体ｍＲＮＡ无表达。研究证实ＩＧＦ－Ⅰ、ＩＧＦ     

胰岛素样生长因子Ⅰ、Ⅱ与其受体mRNA在前列腺增生组织中表达

采用地高辛标记的ｃＲＮＡ探针行细胞原位杂交技术，对良性前列腺增生（ＢＰＨ）组织中胰岛素样生长因子及受体的基因表达情况进行了研究，结果显示：１４／１６例ＢＰＨ组织中ＩＧＦⅠｍＲＮＡ阳性表达，定位在上皮和基质组织；１１／１２例ＢＰＨ组织中，ＩＧＦⅡｍＲＮＡ阳性表达，定位基质；ＩＧＦⅠ受体ｍＲＮＡ在所检测的８例标本中均有表达，主要定位于上皮，而ＩＧＦⅡ受体ｍＲＮＡ无表达。研究证实ＩＧＦⅠ、ＩＧＦⅡｍＲＮＡ在ＢＰＨ组织中都有表达，提示与ＢＰＨ的发病有关。ＢＰＨ组织中ＩＧＦⅠ受体是ＩＧＦ发挥作用的唯一受体，ＩＧＦ通过自分泌和旁分泌方式对前列腺细胞起作用。     

雌、雄激素对前列腺中IGF-I基因表达的影响

目的 探讨雌,雄激素对前列腺中胰岛素样生长因子Ｉ（ＩＧＦ－Ｉ）基因表达的影响,方法 采用斑点杂交结合图像分析技术,观察药物去势和未药物去势ＢＰＨ患者前列腺组织以及正常组,去势组,外源性雄激素组,雌激素组大鼠前列腺组织中ＩＧＦ－Ｉ ｍＲＮＡ表达情况。结果 人体内睾酮水平降低后,前列腺中ＩＧＦ－Ｉ基因表达明显减少;正常大鼠前列腺中ＩＧＦ－ＩｍＲＮＡ表达情况。结果 人体内睾酮水平降低后,前列腺中ＩＧＧＦ     

胰岛素样生长因子—ImRNA在前列腺组织中的表达

对１５例良性前列腺增生和１２例正常前列腺组织标本中胰岛素样生长因了－Ｉ（ＩＧＦ－Ｉ）ｍＲＮＡ的表达情况进行了研究。ＲＴ－ＰＣＲ的方法可自所有标本中检出ＩＧＦ－Ｉ ｍＲＮＡ的表达，并用电泳和Ｓｏｕｔｈｍ杂交证实了结果的可靠性。     

原位杂交检测胰岛素样生长因子I和II在前列腺组织中的表达

为了解胰岛素样生长因子Ｉ和Ⅱ在正常和增生前列腺组织中的表达情况，作者利用分子原位杂交的方法对正常和良性增生的前列腺组织中ＩＧＦ－Ｉ和ＩＧＦ－Ｉ的ｍＲＮＡ的表达情况进行了研究。结果表明，正常和增生的前列腺组织中均有ＩＧＦ－Ｉ和ＩＧＦ－ＩＩｍＲＮＡ的表达。ＩＧＦ－Ｉ主要由上皮细胞，尤其是基底细胞表达，ＩＧＦ－ＩＩ则主要由间质细胞表达，上皮细胞罕有表达。ＢＰＨ组织中ＩＧＦ－Ｉ和ＩＧＦ－Ｉ的表达水平均高于正常前列腺。ＩＧＦ－Ｉ和ＩＧＦ－Ｉ可能在前列腺的生长调节以及良性前列腺增生的发生中发挥着重要作用。     

BPH组织中雄激素受体与转化生长因子—βI型受体表达的相关？…

探讨雄激素受体与转化生长因子－βＩ型受体在良性前列腺增生组织中表达的意义及其相关性。方法采用免疫组化法研究两种受体在３１例ＢＰＨ和２２例正常前列腺本本中表达的状况。结果ＡＲ和ＴＧＦ－βＲＩ在ＢＰＨ上皮,间质组织中的表达显著高于正常前列腺组织;在ＢＰＨ间质组织中ＡＲ和ＴＧＦ－βＲＩ的表达呈正相关。     

BPH组织中雄激素受体与转化生长因子-βⅠ型受体表达的相关性研究

目的探讨雄激素受体（ＡＲ）与转化生长因子βⅠ型受体（ＴＧＦβＲⅠ）在良性前列腺增生（ＢＰＨ）组织中表达的意义及其相关性。方法采用免疫组化法研究两种受体在３１例ＢＰＨ和２２例正常前列腺标本中表达的状况。结果ＡＲ和ＴＧＦβＲⅠ在ＢＰＨ上皮、间质组织中的表达显著高于正常前列腺组织（Ｐ＜００５）;在ＢＰＨ间质组织中ＡＲ和ＴＧＦβＲⅠ的表达呈正相关（相关系数ｒ＝０３５８,Ｐ＜００５）。结论ＡＲ和ＴＧＦβＲⅠ在前列腺增生组织中表达增高,两者之间具有协同作用,提示两者在前列腺中的过表达可能参与了ＢＰＨ的发生和病理过程。     

前列腺增生组织中bFGFmRNA表达的意义

目的 探讨前列腺组织中碱性成纤维细胞生长因子（ｂＦＧＦ）基因和蛋白及基受体表达的意义。方法 应用原位分子杂交和免疫组化方法检测３８例前列腺增生（ＢＰＨ）组织和１０例正常前列腺（ＮＰ）组织中ｂＦＧＦｍＲＮＡ、ｂＦＧＦ和ＦＧＦＲ１表达。结果 前列腺间质细胞和上皮细胞中均见ｂＦＧＦｍＲＮＡ、ｂＦＧＦ和ＦＧＦＲ１阳性染色。ＢＰＨ间质细胞中三者表达显著高于ＮＰ组织,但ＢＰＨ与ＮＰ上皮细胞中三者表达无显著性。     

转化生长因子βⅠ型受体在BPH组织中的表达及意义

目的：探讨转化生长因子βⅠ型受体（ＴＧＦ－βＲ１）在良性前列腺增生症（ＢＰＨ）组织中表达的意义。方法：采用免疫组织化学方法研究ＴＧＦ－βＲ１在３１例ＢＰＨ组织中的表达。结果：ＴＧＦ－βＲ１在ＢＰＨ上皮、间质组织中的表达率显著高于正常前列腺组织（Ｐ〈０．０５）。结论：ＴＧＦ－βＲ１在ＢＰＨ组织中表达增高,尤其在上皮组织中的过度表达可能影响了ＴＧＦ－β对前列腺上皮细胞的抑制作用,可能参与了ＢＰＨ的病理     

前列腺增生和前列腺癌组织细胞调亡及Bc1—2,Bax基因表达？…

目的 探讨良性前列腺增生（ＢＰＨ）和前列腺癌（Ｐｃａ）组织细胞增殖和调亡及Ｂｃ１－２、Ｂａｘ蛋白表达的临床意义。方法 用核酸末端原位标记方法检测ＢＰＨ和Ｐｃａ标本各２３例及５例正常前列腺（ＮＰ）标本,观察细胞调亡情况。用ＡＢＣ免疫组化法研究三种组织中ＰＣＮＡ、Ｂｃ１－２、Ｂａｘ表达及特征。结果 ＢＰＨ和Ｐｃａ的增殖细胞指数（ＰＩ）及调亡细胞指数（ＡＩ）较ＮＰ明显增高（Ｐ〈０．０１）,但ＡＩ／ＰＩ却     

前列腺组织中EGF、bFGF的表达

目的：研究EGF、bFGF在前列腺组织中的表达。方法：应用mRNA斑点杂交、原位杂交、免疫组织化学及原位杂交与免疫组织化学双染法检测6例正常前列腺（NP）、27例良性前列腺增生症（BPH）前列腺组织中EGF及bFGF的表达。结果：BPH前列腺组织和NP组织中无均无EGF mRNA表达,EGF蛋白表达呈弱阳性,两组间差异无显著性意义（P＞0.05）;NP组织上皮细胞有较多bFGF mRNA表达,但无bFGF翻译,基底基质细胞有少量mRNA及蛋白表达,二者表达水平基本一致;BPH前列腺组织上皮细胞无bFGF mRNA表达,但局灶性增殖上皮细胞细胞膜上有bFGF,基底基质细胞有大量bFGF mRNA转录及蛋白质翻译,以局灶性增殖区最为明显。结论：NP及BPH的前列腺组织中无EGF分泌细胞;bFGF在前列腺基底基质细胞过度表达,以自分泌、旁分泌方式促进了基质和上皮的非均一性增殖。     

前列腺衰老逃逸现象的实验研究

目的探讨良性前列腺增生(BPH)衰老逃逸现象的机理。方法采用端粒重复片段扩增法(TRAP)分别检测13例正常前列腺组织、35例BPH组织及33例增生结节和包膜的端粒酶活性表达情况,比较端粒酶活性水平与BPH衰老逃逸的关系。结果正常前列腺组织中端粒酶阳性2例(15%),BPH组织中端粒酶阳性17例(49%),增生结节端粒酶阳性14例(42%),包膜阳性1例(3%);BPH组织端粒酶阳性表达率高于正常前列腺组织(P<0.05),增生结节阳性率明显高于包膜组织(P<0.01)。结论BPH组织中端粒酶活性升高,且分布不均匀。提示前列腺衰老逃逸可能与端粒酶活性有关。     

Caspase-1在良性前列腺增生组织中的表达及意义

目的:探讨正常和良性前列腺增生(BPH)组织中的caspase-1表达情况及意义。方法:应用免疫组化SP法分别检测21例BPH组织和7例正常前列腺组织标本中caspase-1的表达。结果:caspase-1阳性表达率在BPH组织中为71.4%(15/21),正常前列腺组织中为100%(7/7)。BPH上皮组织和间质组织的caspase-1阳性表达均比正常前列腺明显减少(P<0.01)。在BPH组织内部,上皮的caspase-1阳性表达明显高于间质(P<0.01)。结论:caspase-1在BPH组织中的表达较正常前列腺组织显著减少,提示由caspase-1介导的凋亡过程的减少可能参与了BPH的发病过程。     

Differential expression of interleukin-15, a pro-inflammatory cytokine and T-cell growth factor, and its receptor in human prostate.

BACKGROUND: Pro-inflammatory interleukin (IL)-15 plays a major role in host defense and chronic inflammation by stimulating T-lymphocyte recruitment and growth. Expression of IL-15 and IL-15 receptor (IL-15R) in human prostate was examined. METHODS: Normal and benign hyperplastic (BPH) prostate specimens (n = 23) were analyzed for IL-15 and IL-15Ralpha-chain expression by immunohistochemistry and Real-Time-PCR/RT-PCR. Regulation of prostatic stromal cell (PSC) IL-15 mRNA and effect of IL-15 on prostatic cell growth were analysed in vitro. RESULTS: In normal prostate, anti-IL-15 and anti-IL-15Ralpha-chain reactivity were restricted to smooth muscle and stromal cells. However, in BPH, in addition epithelial cells frequently exhibited discrete anti-IL-15R and often intense, membranous anti-IL-15 reactivity. IL-15/IL-15R mRNA were detected in all prostatic cells types. In BPH tissues, IL-15 mRNA content was variable (15-fold). IL-15 mRNA synthesis of PSC was significantly up-regulated by IFN-gamma. Furthermore IL-15 strongly stimulated the growth of BPH-T-lymphocytes and weakly that of carcinoma cell lines, but not of stromal cells. CONCLUSIONS: Overexpression of IL-15 and IL-15Ralpha-chain in BPH and massive proliferation of BPH-T-lymphocytes induced by IL-15 suggest a role for IL-15 in prostatic inflammation. Since IFN-gamma, a T-lymphocyte product, stimulates prostatic IL-15 production; chronic inflammation might be triggered by this paracrine loop.     

Expression of a human cell adhesion molecule, MUC18, in prostate cancer cell lines and tissues

BACKGROUND: Over expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. METHODS: RT-PCR and Western blot analyses were used to analyze the expression of MUC18 mRNA and protein in four human prostate cancer cell lines, cultured primary normal prostate epithelial cells, normal prostate and malignant prostate tissues. Immunohistochemistry was used to determine the expression of MUC18 antigen in prostatic tissues at different stages of malignancy. RESULTS: Human MUC18 mRNA and protein was expressed in three different prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one prostate cancer cell line (LNCaP.FGC). HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from either cultured primary normal prostatic epithelial cells or the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas and in cells of a lymph node metastasis compared to that in normal or benign hyperplastic epithelium (BPH). CONCLUSIONS: We therefore conclude that MUC18 is expressed at higher levels in pre-malignant and malignant prostatic epithelium, including metastasis. We suggest that over-expression of MUC18 may be a new marker of human prostate cancer and also implicates its possible role in development and progression of prostate cancer.     

Expression and immunolocalisation of neutral endopeptidase in prostate cancer

BACKGROUND: Neutral Endopeptidase (NEP) is a cell surface enzyme that cleaves and inactivates neuropeptides. When present on androgen-dependent prostate cancer (PC) cells, NEP inactivates growth stimulatory neuropeptides. After androgen ablation NEP expression decreases and neuropeptides can enhance cell growth, leading to the development of androgen-independent, neuropeptide stimulated PC. Aim of the study was to analyse the expression, localisation and distribution of NEP in benign and malignant prostatic tissues and its relation to the cytoskeleton. METHODS: Immunohistochemistry (IHC) was performed to localise NEP in fixed specimens from normal prostatic tissue, benign prostate hyperplasia (BPH) and PC of Gleason grade 2-5. In situ hybridisation and Western blotting experiments were carried out to confirm NEP gene expression and translation to mature protein in BPH and PC tissue. Confocal laser scanning microscopy was utilised to investigate whether development of high grade prostate tumours was accompanied by changes in intracellular actin/NEP colocalisation patterns. Finally, the proliferative activity in relation to loss of NEP expression was investigated by dual staining of NEP and Ki-67 in prostatic tumours. RESULTS: In situ hybridisation studies revealed preserved expression of NEP mRNA in epithelial cells of PC. NEP was by IHC shown to be located in the apical plasma membrane of normal epithelial cells and BPH tissue. In PC a Gleason grade dependent shift of the NEP distribution pattern towards a heterogeneous, partly cytoplasmic allocation of the protein was found. Compared to BPH tissue, specimens derived from PC showed very low IHC-staining intensity for NEP protein. In high grade PC the typical apical colocalisation of actin and NEP was lost and a strong granular cytoplasmic NEP staining was found. PC areas with a high expression of NEP displayed diminished proliferative activity i.e. low staining intensity for Ki-67. CONCLUSIONS: NEP is differentially expressed in the normal and the pathologically altered prostate with a clear shift from a membrane bound to a cytoplasmic distribution pattern in high-grade tumours and loss of NEP expression in areas of high proliferative activity. The data presented support an active involvement of NEP in the progression of androgen-independent PC. Further studies are needed to unravel the mechanisms underlying the cytoplasmic NEP distribution in PC.