TUMOR SUPPRESSOR ACTIVITIES OF ETS1 GENE PRODUCTS
TUMOR SUPPRESSOR ACTIVITIES OF ETS1 GENE PRODUCTS
批准号:
5201556
负责人:
J LAUTENBERGER
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
DNA binding protein breast neoplasms carcinogenesis inhibitor colon neoplasms gene expression human tissue molecular oncology mutant neoplasm /cancer genetics neoplastic cell prostate neoplasms protein structure function protooncogene tissue /cell culture transcription factor transfection tumor suppressor genes
中文摘要
我们异位表达了转录因子Ets!在两个不同的地方
高致瘤性人结肠癌细胞株DLD-1和HCT116,
不表达内源性ETS1蛋白,并已获得几个
独立克隆人。野生型ETS1蛋白在这些细胞中的表达
结肠癌细胞逆转转化表型和致瘤性
以剂量依赖的方式。相比之下,在DLD-1细胞中的表达
ETS1的一个变体,缺乏转录活性,没有改变
细胞的致瘤特性,表明细胞的减少
这些克隆的致瘤性是野生型ETS1所特有的
基因产品。DLD-1野生型ETS1转染体生长缓慢
无血清培养比表达突变ETS1蛋白的DLD-1细胞缺乏
转录活动。此外,DLD-1野生型ETS1
与DLD-1相比,转基因细胞在细胞周期的G0/G1期停留时间更长
突变型ETS1转染体。这些结果表明,ETS1蛋白在
适当的条件可能会干扰结肠癌细胞的生长。
鉴定ETS1与肿瘤抑制相关的功能结构域
函数,我们已经生成了ETS1的变体,其中缺少
转录活性或DNA结合活性。实验是
突变ETS1蛋白在结肠、乳腺和前列腺中的表达研究进展
以及确定“最小的ETS1区域”负责
用于抑制结肠癌细胞的致瘤性。
英文摘要
We have ectopically expressed transcription factor ETS! in two different
highly tumorigenic human colon cancer cell lines, DLD-1 and HCT116, that
do not express endogenous ETS1 protein and have obtained several
independent clones. The expression of wild-type ETS1 protein in these
colon cancer cells reverses the transformed phenotype and tumorigenicity
in a dose-dependent manner. By contrast, expression in DLD-1 cells of
a variant form of ETS1, lacking transcriptional activity, did not alter
the tumorigenic properties of the cells, suggesting that the reduction
in tumorigenicity in these clones was specific for the wild-type ETS1
gene products. DLD-1 wild-type ETS1 transfectants grow much slower in
serum-free media than DLD-1 cells expressing mutant ETS1 proteins lacking
transcriptional activities. Furthermore, DLD-1 wild-type ETS1
transfectants remain longer in G0/G1 stage of the cell cycle than DLD-1
mutant ETS1 transfectants. These results suggest that ETS1 protein under
appropriate conditions may interfere with growth of colon cancer cells.
To identify functional domains of ETS1 involved in tumor suppressor
function, we have generated variant forms of ETS1 lacking either
transcriptional activities or DNA binding activities. Experiments are
in progress to express mutant ETS1 proteins in colon, breast and prostate
cancer cells as well as to identify "minimum region of ETS1" responsible
for suppression of tumorigenicity of colon cancer cells.
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会议论文
BIOCHEMICAL AND FUNCTIONAL PROPERTIES OF THE ETS PROTO-ONCOGENES
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批准号:5201515
-
项目类别:
-
资助金额:$0.0万
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财政年份:--
-
负责人:J LAUTENBERGER
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依托单位:
ETS ONCOGENE EXPRESSION IN BACTERIA AND YEAST
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批准号:3916926
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J LAUTENBERGER
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依托单位:
REAL-TIME ASSESSMENT OF MACROMOLECULAR INTERACTIONS BY SURFACE PLASMON RESONANCE
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批准号:5201598
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J LAUTENBERGER
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依托单位:
MOLECULAR ASPECTS OF COLON EPITHELIUM DIFFERENTIATION AND TUMOR FORMATION
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批准号:3752747
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J LAUTENBERGER
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依托单位:
TRANSGENIC MOUSE MODEL SYSTEM FOR THE ETS-1 AND ETS-2 PROTO-ONCOGENE FUNCTION
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批准号:5201517
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J LAUTENBERGER
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依托单位:
MOLECULAR MARKERS OF HUMAN LIVER CANCER-NOVEL GENES DIFFERENTIALLY EXPRESSED
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批准号:5201562
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J LAUTENBERGER
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依托单位:
海外基金