Conventional and array-based comparative genomic hybridization analyses of novel cell lines harboring HPV18 from glassy cell carcinoma of the uterine cervix.

Conventional and array-based comparative genomic hybridization analyses of novel cell lines harboring HPV18 from glassy cell carcinoma of the uterine cervix.
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DOI:
10.3892/ijo.24.4.977
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发表时间:
2004-04
影响因子:
5.2
通讯作者:
Y. Hirai;Y. Kawamata;N. Takeshima;R. Furuta;T. Kitagawa;T. Kawaguchi;K. Hasumi;S. Sugai;T. Noda
Y. Hirai;Y. Kawamata;N. Takeshima;R. Furuta;T. Kitagawa;T. Kawaguchi;K. Hasumi;S. Sugai;T. Noda
中科院分区:
医学2区
文献类型:
--
作者:
Y. Hirai;Y. Kawamata;N. Takeshima;R. Furuta;T. Kitagawa;T. Kawaguchi;K. Hasumi;S. Sugai;T. Noda

文献摘要

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我们建立了两个新的人玻璃细胞癌细胞系(GCCOT-1,GCCRK)。这两种细胞系表现出腺和鳞状分化的双重倾向,因此具有类似储备细胞的特征,这是大多数宫颈癌的假定起源。在两种细胞系中均检测到HPV 18型DNA,包括E6-E7,其常见于宫颈鳞状细胞癌以外的细胞类型。我们使用传统的比较基因组杂交(CGH)结合基于阵列的CGH分析了2个细胞系的基因拷贝数改变。在这两种细胞系中证明拷贝数增加的推定癌基因中,在常规宫颈细胞系的先前分析中,1p36.2-1处的FGR(SRC 2)和1 q25 -31处的LAMC 2未报告显示扩增。因此推测这些癌基因与玻璃细胞癌的发生直接相关。另一方面,在这两种细胞系中表现出拷贝数丢失的推定抑制基因中,9 q区域、11q22.3处的ATM和16 q12 -13处的CYLD尚未报道在常规宫颈癌细胞系中表现出丢失。这些位点被推测为与玻璃细胞癌的肿瘤发生直接相关的重要肿瘤抑制因子。这项研究首次表明,连同HPV 18型的存在,在上述位点的改变与玻璃细胞癌,一种特殊类型的宫颈癌的肿瘤发生密切相关。
We established 2 novel human cell lines (GCCOT-1, GCCRK) from glassy cell carcinoma. Both cell lines showed dual tendencies of glandular and squamous differentiation, and thus possess the characteristics resembling reserve cells, the putative origin of most carcinomas arising from the uterine cervix. HPV type 18 DNA including E6-E7, which is commonly found in cell types other than squamous cell carcinoma of uterine cervix, was detected in both cell lines. We analyzed gene copy number alterations of the 2 cell lines using conventional comparative genomic hybridization (CGH) coupled with array-based CGH. Among the putative oncogenes demonstrating copy number gain in both cell lines, FGR(SRC2) at 1p36.2-1 and LAMC2 at 1q25-31 have not been reported to show amplification in previous analyses of conventional cervical cell lines. These oncogenes are thus speculated to be directly associated with oncogenesis of glassy cell carcinoma. On the other hand, among the putative suppressor genes demonstrating copy number loss in both cell lines, the 9q region, ATM at 11q22.3, and CYLD at 16q12-13 have not been reported to show loss in conventional cervical cancer cell lines. These sites are speculated to be important as tumor suppressors directly associated with oncogenesis of glassy cell carcinoma. This study suggests for the first time that together with the presence of HPV type 18, alterations at the above sites are closely associated with oncogenesis of glassy cell carcinoma, a special type of carcinoma in the uterine cervix.