TGFBETA1 IN COLON CANCER PROGRESSION
TGFBETA1 IN COLON CANCER PROGRESSION
批准号:
2417724
负责人:
EILEEN Anne FRIEDMAN
金额:
$22.12万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-07-16 至 2002-04-30
关键词:
中文摘要
在结肠癌发生后,TGFbeta1可以增强他们的
进展到更具侵袭性的状态。我们发现结肠癌
具有高水平的TGFbeta1蛋白的可能性是18倍(p
不到0.0013)进展到转移比低转移的癌症
转化生长因子β1水平。血管内皮生长因子β1水平升高
原发灶维持在淋巴结和转移灶。
这种选择的一种机制是自分泌转化生长因子β1发挥作用
作为一种增长因素。我们将检验这一假设
TGFbeta1-侵袭性和转移性生长刺激
结肠癌细胞是由于诱导低水平的CDK所致
稳定CDK2/Cyclin E复合体的抑制剂p21cip1和
增加它们的激酶活性,并确定其机制
控制这些细胞中p21cip1的水平。TGFbeta1信号转导
随着结肠癌细胞向更大的恶性进展而发生变化。
当TGFbeta1发起信令时,RAS被瞬时激活
导致分化和生长停滞的途径,而不是何时
TGFbeta1刺激细胞生长侵袭。我们将决定
是否通过稳定的显性转染法阻断RAS
阴性的N17rasH将阻断TGFbeta1诱导的成熟和/或
生长抑制。杯状细胞产生粘蛋白,是
第二丰富的结肠上皮细胞类型。我们会
确定结肠杯状细胞不敏感的机制
转化生长因子β1是由于β-多糖形式的水平降低所致
TbetaRIII通过转染法研究。
英文摘要
After colon cancer have developed, TGFbeta1 can enhance their
progression to more invasive states. We found that colon cancers
with high levels of TGFbeta1 protein were 18 times more likely (p
less than 0.0013) to progress to metastases than cancers with low
TGFbeta 1 levels. Elevated levels of TGFbeta 1 found in the
primary tumor were maintained in lymph nodes and metastases.
One mechanism for this selection is that autocrine TGFbeta 1 acts
as a growth factor. We will test the hypothesis that the
TGFbeta1-growth stimulation seen in aggressive and metastatic
colon carcinoma cells is due to induction of low levels of the CDK
inhibitor p21cip1 which stabilize cdk2/cyclin E complexes and
increase their kinase activity, and determine the mechanisms for
controlling p21cip1 levels in these cells. TGFbeta1 signaling
changes as colon carcinoma cells progress to greater malignancy.
Ras is transiently activated when TGFbeta1 initiates a signaling
pathway leading to differentiation and growth arrest, not when
TGFbeta1 stimulates cell growth the invasion. We will determine
whether blocking ras by stable transfection of the dominant
negative N17rasH will block TGFbeta1-induced maturation and/or
growth inhibitition. Goblet cells produce mucins and are the
second most abundant colon epithelial cell-type. We will
determine whether the mechanism of colon goblet cell insensitivity
to TGFbeta 1 is due to reduced levels of the betaglycan form of
TbetaRIII by transfection studies.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
A Novel ROS Controlling Kinase
-
批准号:8035473
-
项目类别:
-
资助金额:$16.79万
-
财政年份:2010
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
A Novel ROS Controlling Kinase
-
批准号:7894135
-
项目类别:
-
资助金额:$20.62万
-
财政年份:2010
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
TGFBETA1 IN COLON CANCER PROGRESSION
-
批准号:6172698
-
项目类别:
-
资助金额:$24.18万
-
财政年份:1997
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
TGFBETA1 IN COLON CANCER PROGRESSION
-
批准号:6376540
-
项目类别:
-
资助金额:$24.74万
-
财政年份:1997
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
TGFBETA1 IN COLON CANCER PROGRESSION
-
批准号:2896203
-
项目类别:
-
资助金额:$23.47万
-
财政年份:1997
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
TGFBETA1 IN COLON CANCER PROGRESSION
-
批准号:2700766
-
项目类别:
-
资助金额:$22.79万
-
财政年份:1997
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
P57 MAP KINASE
-
批准号:2111088
-
项目类别:
-
资助金额:$25.42万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
P57 MAP KINASE
-
批准号:2683605
-
项目类别:
-
资助金额:$27.49万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
Mirk Kinase in Colon Cancer Development
-
批准号:6512881
-
项目类别:
-
资助金额:$27.99万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
Mirk Kinase in Colon Cancer Development
-
批准号:6325006
-
项目类别:
-
资助金额:$27.99万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
Mirk Kinase in Colon Cancer Development
-
批准号:6633139
-
项目类别:
-
资助金额:$27.99万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
P57 MAP KINASE
-
批准号:2390878
-
项目类别:
-
资助金额:$26.43万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
Mirk Kinase in Colon Cancer Development
-
批准号:6871323
-
项目类别:
-
资助金额:$27.99万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
Mirk Kinase in Colon Cancer Development
-
批准号:6724768
-
项目类别:
-
资助金额:$27.99万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
P57 MAP KINASE
-
批准号:2111087
-
项目类别:
-
资助金额:$25.53万
-
财政年份:1995
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
TUMOR PROMOTER INDUCED PROTEIN PHOSPHORYLATION
-
批准号:3195287
-
项目类别:
-
资助金额:$22.35万
-
财政年份:1990
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
TUMOR PROMOTER INDUCED PROTEIN PHOSPHORYLATION
-
批准号:3195286
-
项目类别:
-
资助金额:$15.46万
-
财政年份:1990
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
TUMOR PROMOTER INDUCED PROTEIN PHOSPHORYLATION
-
批准号:3195282
-
项目类别:
-
资助金额:$16.16万
-
财政年份:1990
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
MALIGNANT TO BENIGN TUMOR TRANSITION
-
批准号:3189055
-
项目类别:
-
资助金额:$7.34万
-
财政年份:1987
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
MALIGNANT TO BENIGN TUMOR TRANSITION
-
批准号:3189060
-
项目类别:
-
资助金额:$26.07万
-
财政年份:1987
-
负责人:EILEEN Anne FRIEDMAN
-
依托单位:
海外基金