Identification and validation of genes involved in cervical tumourigenesis.
Identification and validation of genes involved in cervical tumourigenesis.
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DOI：
10.1186/1471-2407-11-80
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发表时间：
2011-02-22
期刊：
影响因子：
3.8
通讯作者：
Selvaluxmy G
中科院分区：
文献类型：
--
作者：
Rajkumar T;Sabitha K;Vijayalakshmi N;Shirley S;Bose MV;Gopal G;Selvaluxmy G
子宫颈癌是印度妇女中最常见的癌症。这种癌症有明确的癌前阶段，并在10-15年或更长时间内发展。本研究旨在鉴定正常、发育不良和浸润性宫颈癌之间的差异表达基因。共28例浸润性宫颈癌，4例CIN3/CIS， 4例CIN1/CIN2, 5例正常宫颈。我们使用微阵列技术，然后通过Taqman低密度阵列实时PCR相对定量验证重要基因。采用免疫组化方法研究MMP3、UBE2C和p16蛋白在宫颈正常、非典型增生和癌组织中的表达。使用MTT法评估显性阴性UBE2C对SiHa细胞生长的影响。我们的研究首次发现宫颈癌中20个基因上调，14个基因下调，5个基因在CIN3中上调。此外，我们的研究也证实了其他研究发现的26个在宫颈癌中起作用的基因。与Normal和CIN1/CIN2相比，UBE2C、CCNB1、CCNB2、PLOD2、NUP210、MELK、CDC20基因在肿瘤和CIN3/CIS中均过表达，表明它们可能在肿瘤发生的早期阶段发挥作用。il - 8、INDO、ISG15、ISG20、agn、DTXL、MMP1、MMP3、CCL18、TOP2A和STAT1在肿瘤中上调。通过免疫组织化学，我们发现与正常宫颈上皮和不同程度的不典型增生相比，癌症中MMP3、UBE2C和p16过表达。在SiHa细胞中发现显性阴性UBE2C产生生长抑制，其UBE2C过表达量是HEK293细胞的4倍。在宫颈癌中发现了几个新基因的差异表达。免疫组化证实宫颈癌组织中MMP3、UBE2C、p16蛋白过表达。这些将需要在更大的样品系列中进一步验证。UBE2C可进一步评估其作为宫颈癌治疗靶点的潜力。
Cervical cancer is the most common cancer among Indian women. This cancer has well defined pre-cancerous stages and evolves over 10-15 years or more. This study was undertaken to identify differentially expressed genes between normal, dysplastic and invasive cervical cancer. A total of 28 invasive cervical cancers, 4 CIN3/CIS, 4 CIN1/CIN2 and 5 Normal cervix samples were studied. We have used microarray technique followed by validation of the significant genes by relative quantitation using Taqman Low Density Array Real Time PCR. Immunohistochemistry was used to study the protein expression of MMP3, UBE2C and p16 in normal, dysplasia and cancers of the cervix. The effect of a dominant negative UBE2C on the growth of the SiHa cells was assessed using a MTT assay. Our study, for the first time, has identified 20 genes to be up-regulated and 14 down-regulated in cervical cancers and 5 up-regulated in CIN3. In addition, 26 genes identified by other studies, as to playing a role in cervical cancer, were also confirmed in our study. UBE2C, CCNB1, CCNB2, PLOD2, NUP210, MELK, CDC20 genes were overexpressed in tumours and in CIN3/CIS relative to both Normal and CIN1/CIN2, suggesting that they could have a role to play in the early phase of tumorigenesis. IL8, INDO, ISG15, ISG20, AGRN, DTXL, MMP1, MMP3, CCL18, TOP2A AND STAT1 were found to be upregulated in tumours. Using Immunohistochemistry, we showed over-expression of MMP3, UBE2C and p16 in cancers compared to normal cervical epithelium and varying grades of dysplasia. A dominant negative UBE2C was found to produce growth inhibition in SiHa cells, which over-expresses UBE2C 4 fold more than HEK293 cells. Several novel genes were found to be differentially expressed in cervical cancer. MMP3, UBE2C and p16 protein overexpression in cervical cancers was confirmed by immunohistochemistry. These will need to be validated further in a larger series of samples. UBE2C could be evaluated further to assess its potential as a therapeutic target in cervical cancer.
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