Structure and methylation-associated silencing of a gene within a homozygously deleted region of human chromosome band 8p22
Structure and methylation-associated silencing of a gene within a homozygously deleted region of human chromosome band 8p22
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DOI：
10.1006/geno.1996.0322
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发表时间：
1996-07-01
期刊：
影响因子：
4.4
通讯作者：
Bookstein, R
中科院分区：
文献类型：
--
作者：
MacGrogan, D;Levy, A;Bookstein, R
位于转移性前列腺癌的同源性缺失区域内的人基因的结构和表达模式已经被表征。通过酵母人工染色体克隆的杂交捕获，分离了该基因的多个cDNA片段，覆盖了缺失区。11个编码外显子跨越730 - 970-kb缺失的205 - 220 kb。预测的氨基酸序列是43%相同的一个匿名的秀丽隐杆线虫基因和20%相同的辅助或调节亚基的寡糖基转移酶复合物在酿酒酵母。所有三种基因产物的疏水性特征是相似的，并且在分子的C-末端半部分中显示出四个推定的跨膜结构域，这表明功能的一般保守性。该基因在包括前列腺、肺、肝和结肠在内的大多数非淋巴样人类细胞/组织中以类似于1.5kb mRNA的形式表达。在许多上皮肿瘤细胞系中检测到表达，但在15个结直肠癌细胞系中的14个、8个肺癌细胞系中的1个和4个肝癌细胞系中的1个中通过北方印迹或RT-PCR检测不到表达。肿瘤细胞系中表达的缺乏与位于该基因5 '端的CpG岛的高甲基化高度相关。这些发现为进一步研究这一候选肿瘤抑制基因奠定了基础。(C)出版社：Academic Press，Inc.
The structure and expression pattern of a human gene located within a homozygously deleted region of a metastatic prostate cancer have been characterized. Multiple cDNA fragments of this gene were isolated by hybrid capture with yeast artificial chromosome clones covering the deletion region. Eleven coding exons spanned 205-220 kb of the 730- to 970-kb deletion. The predicted amino acid sequence was 43% identical to that of an anonymous Caenorhabditis elegans gene and 20% identical to an accessory or regulatory subunit of the oligosaccharyltransferase enzyme complex in Saccharomyces cerevisiae. Hydrophobicity profiles of all three gene products were similar and showed four putative membrane-spanning domains in the molecules' C-terminal halves, suggesting a general conservation of function. The gene was expressed as an similar to 1.5kb mRNA in most nonlymphoid human cells/tissues including prostate, lung, liver, and colon. Expression was detected in many epithelial tumor cell lines, but was undetectable by Northern blot or RT-PCR in 14 of 15 colorectal, 1 of 8 lung, and 1 of 4 liver cancer cell lines. Lack of expression in tumor cell lines was highly correlated with hypermethylation of a CpG island located at the gene's 5' end. These findings form a basis for further work on this candidate tumor suppressor gene. (C) 1996 Academic Press, Inc.