Coxsackie and adenovirus receptor promotes adenocarcinoma cell survival and is expressionally activated after transition from preneoplastic precursor lesions to invasive adenocarcinomas
Coxsackie and adenovirus receptor promotes adenocarcinoma cell survival and is expressionally activated after transition from preneoplastic precursor lesions to invasive adenocarcinomas
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DOI：
10.1158/1078-0432.ccr-04-2370
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发表时间：
2005-06-15
影响因子：
11.5
通讯作者：
Runnebaum, IB
中科院分区：
文献类型：
--
作者：
Brüning, A;Stickeler, E;Runnebaum, IB
目的：细胞粘附蛋白柯萨奇和腺病毒受体（CAR）在人多种腺癌中的差异表达。我们分析了不同CAR表达在腺癌发生和细胞存活中的作用。实验设计：在小鼠乳腺癌模型中，将同基因肿瘤前乳腺组织植入同基因雌性BALB/c小鼠乳腺脂肪垫。采用半定量逆转录pcr技术检测CAR在癌前非侵袭性前体病变和发展中的侵袭性腺癌中的表达。生成过表达CAR的细胞克隆，并通过逆转录- pcr和Western blot分析检测其对凋亡因子的反应和凋亡相关蛋白的表达。结果：在肿瘤前病变与已建立的腺癌相比，在所有存活并转化为浸润性腺癌的6个组织中，CAR的表达增强了2- 5倍。将稳定的car -过表达的人癌细胞系HeLa、CaSki和A2780细胞克隆与亲本细胞系进行比较，应用肿瘤坏死因子相关的凋亡诱导配体或生长因子退出后，细胞存活率增加1.5- 6倍。car增强的细胞存活伴随着caspase 3激活的降低和bcl-2或bcl-XL表达的增强，这取决于所测试的细胞类型。bcl-2在所有表达car的小鼠腺癌模型中均表达上调。结论：CAR的表达在肿瘤前病变向肿瘤性乳腺癌转移后增强。CAR表达增强可促进癌细胞存活。这些数据提示CAR的差异表达是肿瘤发生的一个新因素。
Purpose: The cell adhesion protein, coxsackie and adenovirus receptor (CAR), is differentially expressed in various human adenocarcinomas. We analyzed the role of differential CAR expression during tumorigenesis and in cell survival of adenocarcinomas.Experimental Design: In a murine mammary cancer model, a syngenic preneoplastic mammary tissue was implanted into the mammary fat pads of syngenic female BALB/c mice. CAR expression was determined by semiquantitative reverse transcription-PCR in the preneoplastic noninvasive precursor lesions and the developing invasive adenocarcinomas. Cell clones overexpressing CAR were generated and tested for their response to apoptotic factors and for the expression of apoptosis relevant proteins by reverse transcription-PCR and Western blot analysis.Results: In comparison of preneoplastic precursor lesions with established adenocarcinomas, CAR expression was enhanced 2- to 5-fold in all six tissues which had survived and transformed into invasive adenocarcinomas. When stable CAR-overexpressing cell clones of the human cancer cell lines HeLa, CaSki, and A2780 were compared with the parental cell lines, 1.5- to 6-fold more cells survived application of tumor necrosis factor-related apoptosis-inducing ligand or growth factor withdrawal. CAR-enhanced cell survival was accompanied by reduced activation of caspase 3 and enhanced expression of bcl-2 or bcl-XL, depending on the cell type tested. Upregulation of bcl-2 was found in all CAR-expressing adenocarcinomas of the murine cancer model.Conclusions: CAR expression is enhanced after transition from preneoplastic precursor lesions to neoplastic mammary cancer outgrowths. Enhanced CAR expression can promote cancer cell survival. These data suggest differential expression of CAR as a new factor in tumorigenesis.