肿瘤相关粘蛋白MUC1及其mRNA与卵巢上皮性肿瘤关系的研究

目的 :初步探讨肿瘤相关粘蛋白MUC1基因及其蛋白与卵巢上皮性肿瘤的关系。方法 :采用原位杂交法和免疫组化ABC法 ,检测 6 5例卵巢上皮性肿瘤组织和 8例正常卵巢组织MUC1mRNA及其蛋白的表达。结果 :MUC1mRNA和MUC1阳性表达皆位于胞浆和胞膜 ,多呈灶状分布。MUC1mRNA和MUC1在卵巢癌中的检出率分别为 75 .6 % ,80 .0 % ,显著高于良性上皮性肿瘤的 4 0 % ,4 5 %和正常卵巢组织的 2 5 .0 % ,37.5 % (P <0 .0 0 5 )。二者高表达与卵巢癌的期别晚、组织分化差及淋巴结转移有关。结论 :MUC1作为新型肿瘤标志物 ,与卵巢癌的发生、发展密切相关     

肿瘤相关粘蛋白MUCl及其同种型MUCl／Y与卵巢上皮性肿瘤关系的研究

目的 探讨肿瘤相关粘蛋白MUCl及其同种型MUC1／Y粘蛋白在卵巢上皮性肿瘤的变化特征。方法 采用免疫组化ABC法，对72例卵巢上皮性、桨液性和粘液性肿瘤组织和8例正常卵巢组织MUCl和MUCl／Y粘蛋白进行检测。结果 MUCl在卵巢癌中的表达率(80％)高于良性上皮性肿瘤(45％)和正常卵巢组织(37.5％)，P＜0．005。MUCl／Y仅在卵巢癌中表达，二者高表达，与卵巢癌的恶性程度高、组织分化差、癌瘤播散及淋巴结转移有关。结论 MUCl、MUC1／Y作为一种新型的肿瘤标志物，与卵巢癌的发生、发展密切相关。     

MUC1在上皮性卵巢癌中的表达及临床价值

目的:检测黏蛋白1(MUC1)在上皮性卵巢癌组织中的表达情况及其与上皮性卵巢癌临床病理特征和预后的关系,并结合数据库分析其在卵巢癌患者诊断和治疗中的临床价值。方法:收集2015～2016年山东大学齐鲁医院收治的51例上皮性卵巢癌组织及14例正常卵巢组织,组织标本均经HE染色证实符合病理要求,采用免疫组化法检测MUC1蛋白表达。结合数据库分析MUC1表达与临床病理特征的相关性。结果:免疫组化验证MUC1蛋白在上皮性卵巢癌中阳性表达率[52.9%(27/51)]显著高于正常卵巢组织[7.1%(1/14)]。上皮性卵巢癌组织中MUC1蛋白表达与FIGO分期呈正相关(P=0.019),但与患者年龄、肿瘤组织学类型、分化、转移、腹水等无明显相关(P0.05)。总生存期分析显示,MUC1蛋白表达阴性组的预后明显好于MUC1蛋白阳性组(P=0.0308)。以上结果与数据库分析RNA水平MUC1表达相一致,数据库分析还提示MUC1表达可能与化疗耐药相关。结论:上皮性卵巢癌中MUC1表达与分期相关,预示卵巢癌患者预后不良,可作为上皮性卵巢癌的预后预测因子和治疗的新靶标。     

卵巢上皮性肿瘤中黏蛋白MUC2和MUC5AC的表达及意义

目的 研究卵巢上皮性肿瘤中黏蛋白MUC2和MUCSAC的表达，探讨它们在卵巢上皮性肿瘤恶性进展中的作用及其临床意义。方法 采用免疫组化方法SP法检测20例良性、23例交界性和37例恶性卵巢上皮性肿瘤中黏蛋白MUC2和MUCSAC的表达。结果 黏蛋白MUC2和MUCSAC表达水平随卵巢黏液性肿瘤恶性程度的增加而表达增高。黏蛋白MUC2的表达与肿瘤的病理分级和临床分期密切相关，而黏蛋白MUCSAC与病理分级和临床分期无关。结论 卵巢黏液性肿瘤发生早期肿瘤细胞即有胃型和肠型的分化，并且随着肿瘤的恶性进展持续存在。检测黏蛋白MUC2的表达可作为预测卵巢癌预后的有价值的指标。。     

子宫中粘蛋白MUC1的研究进展

正常生理情况下粘蛋白MUC1在子宫内膜容受期的丢失受类固醇激素、胚泡的影响,并发现一些MUC1脱落酶.MUC1在子宫调节胚泡植入中发挥抑制和促进两方面作用.该蛋白异常表达可致女性不孕.子宫恶性肿瘤时,发现MUC1和雌激素受体(ER)α相关.肿瘤相关MUC1比正常MUC1在结构上显示明显改变.MUC1可以和参与肿瘤转化和细胞黏附的各种蛋白相互作用.子宫内膜癌MUC1表达丢失和预后好相关.     

上皮性卵巢癌组织中MRP-1/CD9的表达及临床意义

目的探讨运动相关蛋白MRP-1/CD9在上皮性卵巢癌组织中的表达及临床意义.方法 2004年1～11月中国医科大学附属第二医院应用半定量RT-PCR方法,检测MRP-1/CD9mRNA在36例上皮性卵巢癌、6例交界性卵巢肿瘤、8例良性上皮性卵巢肿瘤和8例正常卵巢组织中的表达.结果 MRP-1/CD9mRNA在上皮性卵巢癌和交界性卵巢肿瘤组织中的表达率和表达强度分别为(33.3%,0.63±0.47)和(66.7%,1.10±0.40),与正常卵巢(100%,1.66±0.31)和卵巢良性肿瘤(100%,1.52±0.29)相比明显降低(P<0.05), 其在卵巢癌中的表达率和表达强度均与肿瘤分期呈负相关(P<0.05),而与组织分级和病理类型无关(P>0.05).结论 MRP-1/CD9的表达缺失在上皮性卵巢癌的发生、发展、浸润过程中起重要的作用,可作为卵巢癌生物学行为的重要指标.     

子宫中粘蛋白MUC1的研究进展

正常生理情况下粘蛋白MUC1在子宫内膜容受期的丢失受类固醇激素、胚泡的影响，并发现一些MUC1脱落酶。MUC1在子宫调节胚泡植入中发挥抑制和促进两方面作用。该蛋白异常表达可致女性不孕。子宫恶性肿瘤时，发现MUC1和雌激素受体（ER）α相关。肿瘤相关MUC1比正常MUC1在结构上显示明显改变。MUC1可以和参与肿瘤转化和细胞黏附的各种蛋白相互作用。子宫内膜癌MUC1表达丢失和预后好相关。     

凝溶胶蛋白、细胞周期蛋白1在卵巢上皮性肿瘤中的表达及其意义

目的:探讨凝溶胶蛋白(gelsolin)、细胞周期蛋白1(cyclinD1)在卵巢上皮性肿瘤的表达情况及其意义.方法:运用免疫组织化学SP法检测65例卵巢癌、18例卵巢交界性肿瘤和24例正常卵巢组织中的gelsolin、cyclinD1的表达情况.结果:gelsolin在卵巢癌(16.9%)和卵巢交界性肿瘤(33.3%)的表达阳性率明显低于正常卵巢组织(75.0%),其差异具有高度统计学意义(P<0.01),而卵巢交界性肿瘤与卵巢癌gelsolin的阳性表达率之间的差异无统计学意义(P>0.05).cyclinD1在正常卵巢组织、交界性肿瘤、卵巢癌的过表达率为8.3%、38.9%、67.7%,3者之间过表达率的差异具有高度统计学意义及统计学意义(P<0.01,P<0.05).而二者与患者的年龄、组织学类型、组织学分级及临床分期等临床病理因素均无统计学相关性(P>0.05).结论:gelsolin表达降低及cyclinD1的过表达与卵巢上皮性肿瘤的发生发展相关,可能是肿瘤发生发展过程中的早期事件.但gelsolin与cyclinD1表达无相关性.     

Nidogen-1、nidogen-2在卵巢上皮性肿瘤组织中的表达及意义

目的:研究巢蛋白(nidogen-1和nidogen-2)在卵巢上皮性肿瘤中的表达,探讨巢蛋白在卵巢上皮性肿瘤侵袭转移过程中作用及临床意义。方法:采用免疫组化法检测21例卵巢上皮性癌、11例卵巢交界性肿瘤和19例良性卵巢肿瘤组织中nidogen-1和nidogen-2的表达情况。结果:nidogen-1和nidogen-2蛋白在卵巢癌中无表达;卵巢良性肿瘤和卵巢交界性肿瘤中nidogen-1阳性表达率分别为73.68%和63.64%,nidogen-2阳性表达率分别为68.42%、54.55%,均显著高于卵巢癌组织(P0.01)。结论:卵巢上皮性肿瘤组织侵袭转移的过程中伴随着基底膜的破坏及nidogen-1和nidogen-2的表达缺失。     

PARP-1与NF-κB在卵巢上皮性肿瘤组织中的表达及意义

目的:研究卵巢上皮性肿瘤组织中聚腺苷酸二磷酸核糖聚合酶-1(PARP-1)、核转录因子κB(NF-κB)的表达及意义.方法:采用免疫组织化学SP法检测10例正常卵巢组织、30例卵巢良性肿瘤、30例卵巢交界性肿瘤和50例卵巢癌原发灶中的PARP-1和NF-κBp65蛋白表达.结果:①PARP-1蛋白和NF-κBp65蛋白在卵巢癌组织中阳性表达率均高于卵巢交界性肿瘤、卵巢良性肿瘤和正常卵巢组织,差异均有统计学意义(P＜0.05);而两者的阳性表达率在卵巢交界性肿瘤、卵巢良性肿瘤及正常卵巢组织间比较,差异均无统计学意义(P＞0.05).②PARP-1和NF-κBp65蛋白与卵巢癌的病理分级、临床分期和有无淋巴结转移有关(P＜0.05).③卵巢癌组织中PARP-1与NF-κBp65表达呈正相关(r=0.596,P＜0.05).结论:PARP-1和NF-κB在卵巢癌组织中过表达,与卵巢癌的发生、发展有关.PARP-1可能通过作用于NF-κB促进卵巢上皮性肿瘤细胞的恶性转化.     

Expression of MUC1 in primary and metastatic human epithelial ovarian cancer and its therapeutic significance

BACKGROUND: MUC1 is associated with cellular transformation and tumorigenicity and is considered as an important tumor-associated antigen (TAA) for cancer therapy. The objective of this study was to evaluate the patterns of MUC1 expression in primary tumors and metastatic lesions in the advanced stages of epithelial ovarian cancers (EOCs) and correlate the expression with clinicopathological features. METHODS: The expression of MUC1 was examined on frozen tissue sections from primary EOC (n=42), the matched metastatic lesions (n=30) and paraffin-embedded tissue sections from primary EOC (n=60), normal ovarian tissues (n=20) using immunohistochemistry (IHC) by monoclonal antibody (MAb) C595. RESULTS: The expression of MUC1 was found in 92% (39/42) of EOC and 90% (27/30) of the matched metastatic lesions in frozen tissue sections respectively while the expression of MUC1 was found in 95% (57/60) of EOC and 5% (1/20) of normal ovarian tissues in paraffin-embedded sections respectively. Most of the tumors showed moderate to strong intensity staining while normal ovarian tissues only showed weak intensity staining. The overexpression of MUC1 was significantly associated with various progression parameters such as tumor stage, grade, residual disease status and presence of ascites (P<0.05). CONCLUSIONS: MUC1 is overexpressed in above 90% of late stage of EOC and of metastatic lesions but not in normal ovarian tissues, and the high expression of MUC1 is correlated with EOC progression. MUC1 antigen may be a useful therapeutic target to prevent the development of incurable, recurrent metastatic EOC.     

Biosynthesis of MUC1 mucin in human endometrial adenocarcinoma is modulated by estradiol and tamoxifen

Polymorphic epithelial mucin MUC1 is expressed by most epithelial cancers ,although free natural MUC1 antibodies are present in the circulation of healthy subjects as well as in that of cancer patients. The role of MUC1 mucin molecules in cancer cells of endometrium is not precisely known. The results reported here demonstrate that MUC1 biosynthesis in human endometrial adenocarcinoma cells (Ishikawa line) is stimulated by estradiol hormone and inhibited by tamoxifen ,which was measured by [¹⁴C]threonine or [³H]glucosamine incorporation into MUC1 protein. Tamoxifen applied in combination with estradiol also inhibited this process ,but pre-incubation of cells with estradiol resulted in a decrease in the inhibitory effect of tamoxifen. Electroblotting and reactions with antibodies against MUC1 core protein epitopes confirmed the presence of MUC1 in cell lysates and culture media of Ishikawa cells. Reactions with lectins showed the presence of oligosaccharide structures demonstrating antigen-T activity and the presence of sialic acid residues. The results confirm that there is downregulation of MUC1 expression in cancer culture cells treated with selective estrogen receptor modulators ,which may be essential for reducing the migration of cancer cells and the metastatic properties of tumor cells.     

Frequent and increased expression of human METCAM/MUC18 in cancer tissues and metastatic lesions is associated with the clinical progression of human ovarian carcinoma

ObjectivesHuman METCAM/MUC18 (huMETCAM/MUC18), a cell adhesion molecule, plays an important role in the progression of several epithelial cancers; however, its role in the progression of epithelial ovarian cancers is unknown. To initiate the study we determined expression of this protein in normal and cancerous ovarian tissues, cystadenomas, metastatic lesions, and ovarian cancer cell lines.Materials and methodsImmunoblotting and immunohistochemical (IHC) methods were used to determine huMETCAM/MUC18 expression in lysates of frozen and formalin-fixed, paraffin-embedded tissue sections of normal human ovaries, and ovarian (benign) cystadenomas, carcinomas and metastatic lesions. We also determined expression levels of several downstream effectors of METCAM/MUC18 in these tissues.ResultsHuMETCAM/MUC18 levels in ovarian carcinomas and metastatic lesions were significantly higher than in normal tissues and cystadenomas. IHC results showed that expression of huMETCAM/MUC18 in normal tissues and cystadenomas was mostly absent from epithelial cells, but in carcinomas and metastatic lesions it was localized to epithelial cells. In higher pathological grades of ovarian cancer and metastatic lesions, the percentage of cells stained in IHC was increased. Thirty percent of normal tissues weakly expressed the huMETCAM/MUC18 antigen, but 70% of cancer tissues and 100% of metastatic lesions expressed the antigen. Expression levels of several downstream effectors of huMETCAM/MUC18, Bcl2, PCNA and VEGF, were elevated in cancerous tissues, however, not that of Bax. The phospho-AKT/AKT ratio was elevated in metastatic lesions.ConclusionUpexpression of huMETCAM/MUC18 may be a marker for the malignant potential of ovarian carcinomas. Progression of ovarian cancer may involve increased signaling in anti-apoptosis, proliferation, survival/proliferation pathway, and angiogenesis.     

Novel MUC1 splice variants are expressed in cervical carcinoma

OBJECTIVES: The MUC1 antigen can be used to identify epithelial cells from the background of hemopoietic cells. The present investigation describes patterns of overexpression of two novel MUC1 splice variants in human cervical carcinoma cell lines. METHODS: RT-PCR was carried out to determine MUC1 splice variants in the cervical cancer cell lines C-4 II, C-33A, DoTc 2 4510, C-4 I, SiHa, HT3, Hs 636 T (C4-I), and HeLa. RESULTS: The novel MUC1 splice variant D was expressed in all cell lines and the novel MUC1 splice variant C was expressed in all cell lines but C-33A. Variants A and B were expressed in all (variant A) and all but one (variant B) cell line. MUC1/REP was expressed in all cell lines and MUC1/SEC was positive in all but two cell lines (C-33 A, DoTc 2 4510). All but one cell line (C-33A) expressed MUC1/X and MUC1/Y, and two cell lines (C-33 A, DoTc 2 4510) did not express MUC1/Z, respectively. MUC1 variants A, D, and REP could be demonstrated consistently among all eight cervical carcinoma cell lines we have examined. CONCLUSIONS: The present study describes the feasibility of detecting a large number of MUC1 variants, including MUC1 variants C and D which are described for cervical carcinoma cells for the first time. Further studies will examine the presence of MUC1 splice variants' expression in human cervical carcinoma tissue.     

MUC16在卵巢癌发生发展中的研究进展

MUC16,又名CA125,是一种表达于各类上皮细胞表面的高分子量糖蛋白,主要发挥保护和修复上皮的作用。MUC16是早期诊断上皮性卵巢癌的重要肿瘤指标,广泛应用于临床。近来研究发现,MUC16的异常表达与卵巢癌的不良预后和发生发展密切相关。MUC16可以通过与间皮素结合促进卵巢癌远处转移,可以通过抑制肿瘤细胞和免疫细胞形成免疫突触帮助卵巢癌细胞实现免疫逃逸。MUC16还可以通过在卵巢癌中的过表达来影响肿瘤细胞的上皮间质转化（EMT）、增殖、迁移和转移,促进卵巢癌的发生发展。尽管有关MUC16与卵巢癌的研究逐渐取得进展,但MUC16的生化结构及其在卵巢癌中具体作用机制仍处于研究阶段。综述MUC16的生化结构及其在卵巢癌细胞的免疫逃逸和卵巢癌增殖、迁移、侵袭和转移中的研究进展,旨在为卵巢癌的治疗提供新的靶点。     

G蛋白耦联受体30(GPR30)在上皮性卵巢癌中的表达与增殖相关基因c-fos、cyclinD1表达的相关性

目的:探索新型雌激素受体G蛋白耦联受体30(G protein coupled receptor 30,GPR30)在人上皮性卵巢癌发生发展中的作用。方法:采用免疫组织化学SP法检测30例上皮性卵巢癌组织中GPR30、增殖相关基因c-fos和cyclinD1的表达,并以9例良性卵巢肿瘤、4例正常卵巢组织作对照。结果:GPR30在上皮性卵巢癌的表达水平(80.0%)显著高于良性卵巢肿瘤(44.4%)和正常卵巢组织(25.0%)(P<0.01;P<0.05)。GPR30和c-fos的表达与上皮性卵巢癌的病理类型、FIGO分期有关,在浆液性囊腺癌、FIGOⅢ-Ⅳ期的表达水平显著升高(P<0.05)。未见cyclinD1的表达与上皮性卵巢癌临床病理参数的关系(P>0.05)。上皮性卵巢癌中GPR30与c-fos、cyclinD1的表达具有正相关性(P<0.01;P<0.05)。结论:GPR30可能通过c-fos、cyclinD1促进卵巢癌增殖,参与上皮性卵巢癌的发生、发展。