S100A11, a putative tumor suppressor gene, is overexpressed in pancreatic carcinogenesis

S100A11, a putative tumor suppressor gene, is overexpressed in pancreatic carcinogenesis
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DOI:
10.1158/1078-0432.ccr-06-0222
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发表时间:
2006-09-15
影响因子:
11.5
通讯作者:
Tanaka, Masao
Tanaka, Masao
中科院分区:
医学1区
文献类型:
--
作者:
Ohuchida, Kenoki;Mizumoto, Kazuhiro;Tanaka, Masao

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目的:最近的芯片分析显示,S100 A11在胰腺癌中表达上调。本研究的目的是评估S100 A11与胰腺癌发生的关系。实验设计:我们通过定量逆转录-PCR检测了与胰腺癌及其前病变、导管内乳头状黏液性肿瘤(IPMN)和胰腺上皮内瘤变相关的各种临床样本中S100 A11 mRNA的表达。胰腺癌(n = 22)和IPMN(n = 18)大块组织中S100 A11的水平显著高于非肿瘤大块组织(n = 22;两者P < 0.0001)。S100 A11的水平在胰腺癌和IPMN大块组织之间没有差异。然而,在显微切割分析中,IPMN细胞(n = 21)表达显著更高水平的S100 A11,然后是癌细胞(n = 23; P = 0.003)。胰腺上皮内瘤变细胞(n = 6)中S100 A11表达的中位数水平高于癌细胞。在胰液分析中,(n = 24; P = 0.004)和IPMN相关(n = 18; P = 0.001)与慢性胰腺炎相关的汁液(n = 23)相比,汁液表达的S100 A11水平显著更高。目前的数据表明,表达S100 A11,一个假定的肿瘤抑制基因,在胰腺癌发生的早期阶段增加,并在随后的癌症进展过程中减少。对胰液中S100 A11水平的分析可能是筛查可能进展为胰腺癌的高危病变患者或检测早期胰腺癌的有效工具。
Purpose: Recent microarray analyses revealed that expression of S100A11 is up-regulated in pancreatic cancer. The aim of the present study was to evaluate the association of S100A11 with pancreatic carcinogenesis.Experimental Design: We measured S100A11 mRNA expression in various clinical samples related to pancreatic cancer and its precursor lesions, intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia, by quantitative reverse transcription-PCR.Results: Levels of S100A11 were significantly higher in pancreatic cancer (n = 22) and IPMN (n = 18) bulk tissues than in nonneoplastic bulk tissues (n = 22; P < 0.0001 for both). Levels of S100A11 did not differ between pancreatic cancer and IPMN bulk tissues. In microdissection analyses, however, IPMN cells (n = 21) expressed significantly higher levels of S100A11 then did cancer cells (n = 23; P = 0.003). The median level of S100A11 expression was higher in pancreatic intraepithelial neoplasia cells (n = 6) than in cancer cells. In pancreatic juice analyses, cancer-related (n = 24; P = 0.004) and IPMN-related (n = 18; P = 0.001) juice expressed significantly higher levels of S100A11 than did chronic pancreatitis - related juice (n = 23).Conclusions: The present data suggest that expression of S100A11, a putative tumor suppressor gene, is increased in the early stage of pancreatic carcinogenesis and decreased during subsequent progression to cancer. Analysis of the S100A11 level in pancreatic juice may be an effective tool for screening of patients with high-risk lesions that could progress to pancreatic cancer or detecting early-stage pancreatic cancer.