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一种p53同源物和一种新型丝氨酸蛋白酶抑制剂在肺鳞状细胞癌中过度表达。

A p53 homologue and a novel serine proteinase inhibitor are over-expressed in lung squamous cell carcinoma.

作者信息

Wang T, Hopkins D A, Fan L, Fanger G R, Houghton R, Vedvick T S, Repasky E, Reed S G

机构信息

Department of Tumor Antigen Discovery, Corixa Corporation, 1124 Columbia Street, Seattle, WA 98104, USA.

出版信息

Lung Cancer. 2001 Dec;34(3):363-74. doi: 10.1016/s0169-5002(01)00260-4.

Abstract

LSCC is a common type of lung cancer and accounts for approximately 30% of all lung cancers. We have used a combination of subtraction and cDNA microarray technology to identify genes preferentially over-expressed in LSCC. Here we report extensive molecular characterization of two novel full-length cDNA sequences, L530S and L531S. Although L530S and L531S were found to be differentially over-expressed in LSCC, the expression profiles for these two genes were not identical. L530S expression was specifically elevated in LSCC whereas L531S transcript was up regulated in both LSCC and head and neck squamous cell carcinoma samples. L530S is a homologue of p53, and L531S belongs to a new member of serine proteinase inhibitors with significant homology to SCCA1 and SCCA2. Furthermore, L531S protein was found to be expressed in lung cancers by IHC analysis. The distinct as well as similar expression profiles exhibited by L530S and L531S suggest that each gene may play a unique role for tumorgenesis of LSCC. Identification of these genes not only allows us to further explore their diagnostic and therapeutic potentials for LSCC, but also provides us with additional tools and reagents for understanding the biology behind LSCC, and differentiating LSCC from other types of lung cancer at the molecular level.

摘要

肺鳞状细胞癌(LSCC)是肺癌的一种常见类型,约占所有肺癌的30%。我们运用消减杂交和cDNA微阵列技术相结合的方法,来鉴定在LSCC中优先过度表达的基因。在此,我们报告两个新的全长cDNA序列L530S和L531S的广泛分子特征。尽管发现L530S和L531S在LSCC中差异过度表达,但这两个基因的表达谱并不相同。L530S的表达在LSCC中特异性升高,而L531S转录本在LSCC和头颈部鳞状细胞癌样本中均上调。L530S是p53的同源物,L531S属于丝氨酸蛋白酶抑制剂的一个新成员,与鳞状细胞癌抗原1(SCCA1)和鳞状细胞癌抗原2(SCCA2)具有显著同源性。此外,通过免疫组化分析发现L531S蛋白在肺癌中表达。L530S和L531S所呈现出的不同以及相似的表达谱表明,每个基因可能在LSCC的肿瘤发生中发挥独特作用。这些基因的鉴定不仅使我们能够进一步探索它们对LSCC的诊断和治疗潜力,还为我们提供了额外的工具和试剂,用于理解LSCC背后的生物学机制,并在分子水平上将LSCC与其他类型的肺癌区分开来。

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