The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression.
The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression.
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TGFBI 在间皮瘤和乳腺癌中的作用：与肿瘤抑制的相关性
DOI：
10.1186/1471-2407-12-239
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发表时间：
2012-06-13
期刊：
影响因子：
3.8
通讯作者：
Hei TK
中科院分区：
文献类型：
--
作者：
Li B;Wen G;Zhao Y;Tong J;Hei TK
背景转化生长因子β诱导产物（transforminggrowthfactor β inducedproduct，TGFBI）是一种细胞外基质（extracellularmatrix，ECM）蛋白，近年来被认为是一种肿瘤抑制因子。我们的前期研究发现，TGF β 1基因在多种肿瘤细胞系和临床组织中表达下调。在这项研究中，TGFBI的异位表达被用来确定其作为一种肿瘤抑制剂的作用，并确定间皮瘤和乳腺cancer.MethodsCells的潜在机制与pRc/CMV 2-TGFBI和pRc/CMV 2-空载体与Lipofectamine Plus稳定转染。采用定量PCR和Western-blotting对TGFBI的异位表达进行定量。使用生长曲线、克隆形成存活率和软琼脂生长来评估细胞活力的表征。采用小鼠体内成瘤模型评价其成瘤潜力。流式细胞仪分析细胞周期。Western-blotting检测p21、p53、p16、p14蛋白表达。通过使用衰老β-半乳糖苷酶染色试剂盒分选衰老细胞。端粒酶活性测定使用定量端粒酶检测试剂盒。ResultsIn这项研究中，异位表达TGFBI在两种类型的癌细胞系，间皮瘤细胞系NCI-H28和乳腺癌细胞系MDA-MB-231被发现有减少细胞生长，平板效率，和锚定非依赖性生长。这些癌细胞系的致瘤性通过裸鼠皮下接种测定，同样受到TGFBI表达的抑制。同样，TGFBI表达减少了S期的比例，而增加了G1期的比例在这些细胞中。TGFBI重新表达后细胞周期的重新分布与p21和p53表达的短暂升高相对应。结论TGF β 1基因转染的细胞衰老相关的β-半乳糖苷酶和端粒酶活性增强，提示TGF β 1基因可能通过抑制细胞增殖、延缓G1-S期转变和诱导衰老而抑制间皮瘤和乳腺癌细胞的生长。
BackgroundTransforming growth factor β induced (TGFBI) product, an extracellular matrix (ECM) protein, has been implicated as a putative tumor suppressor in recent studies. Our previous findings revealed that expression ofTGFBIgene is down-regulated in a variety of cancer cell lines and clinical tissue samples. In this study, ectopic expression of TGFBI was used to ascertain its role as a tumor suppressor and to determine the underlying mechanism of mesothelioma and breast cancer.MethodsCells were stably transfected with pRc/CMV2-TGFBI and pRc/CMV2-empty vector with Lipofectamine Plus. Ectopic expression of TGFBI was quantified by using quantitative PCR and Western-blotting. Characterization of cell viability was assessed using growth curve, clonogenic survival and soft agar growth. The potential of tumor formation was evaluated by anin vivomouse model. Cell cycle was analyzed via flow cytometry. Expressions of p21, p53, p16 and p14 were examined using Western-blotting. Senescent cells were sorted by using a Senescence β-Galactosidase Staining Kit. Telomerase activity was measured using quantitative telomerase detection kit.ResultsIn this study, an ectopic expression of TGFBI in two types of cancer cell lines, a mesothelioma cell line NCI-H28 and a breast cancer cell line MDA-MB-231 was found to have reduced the cellular growth, plating efficiency, and anchorage-independent growth. The tumorigenicity of these cancer cell lines as determined by subcutaneous inoculation in nude mice was similarly suppressed by TGFBI expression. Likewise, TGFBI expression reduced the proportion of S-phase while increased the proportion of G1 phase in these cells. The redistribution of cell cycle phase after re-expression of TGFBI was correspondent with transiently elevated expression of p21 and p53. The activities of senescence-associated β-galactosidase and telomerase were enhanced in TGFBI-transfected cells.ConclusionCollectively, these results imply that TGFBI plays a suppressive role in the development of mesothelioma and breast cancer cells, possibly through inhibitions of cell proliferation, delaying of G1-S phase transition, and induction of senescence.
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影响因子：
3.7
作者：
Lin B;Madan A;Yoon JG;Fang X;Yan X;Kim TK;Hwang D;Hood L;Foltz G
通讯作者：
Foltz G
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
DOI：
10.1016/s0006-291x(02)00576-4
发表时间：
2002-06-28
影响因子：
3.1
作者：
Bae, JS;Lee, SH;Kim, IS
通讯作者：
Kim, IS
影响因子：
8
作者：
Ji, P;Agrawal, S;Müller-Tidow, C
通讯作者：
Müller-Tidow, C
影响因子：
2.5
作者：
Kim, MO;Yun, SJ;Lee, EH
通讯作者：
Lee, EH