CELL SENESCENCE, CARCINOGENESIS, AND AGING
CELL SENESCENCE, CARCINOGENESIS, AND AGING
批准号:
3841060
负责人:
J C BARRETT
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 replication aging carcinogenesis cell age cell cycle proteins cell growth regulation cell senescence cellular oncology embryo /fetus tissue /cell culture fibroblasts gene expression human genetic material tag human tissue messenger RNA neoplastic transformation phosphatase inhibitor phosphoprotein phosphatase phosphorylation protein biosynthesis protein tyrosine kinase tissue /cell culture transfection
中文摘要
然而,癌症仍然是与衰老相关的主要健康问题之一
英文摘要
Cancer remains one of the major health problems associated with aging, yet
the role of the aging process in cancer remains to be determined. One
approach to this problem is to study aging at the molecular level using
cellular models of aging, which may provide insights into both the cancer
and the aging processes. We have shown that defects in the senescence
program in cancer cells can be corrected by introduction of human
chromosome 1 from normal cells into immortal cells. Cellular senescence is
a state of irreversible cell cycle arrest in which normal cells fail to
enter into DNA synthesis upon serum stimulation. We examined whether
proteins required for G1/S cell cycle progression were irreversibly down-
regulated in senescent human fibroblasts. In contrast to young cells where
both forms of MAP-kinase were phosphorylated on tyrosine in response to
serum, the p42MAP-kinase was not tyrosine phosphorylated upon serum
stimulation, whereas p44MAP-kinase was phosphorylated on tyrosine in serum-
starved or serum-stimulated senescent cells. Cdc2 and cyclin A mRNAs were
completely down-regulated in senescent fibroblasts. Clones expressing the
transfected human cyclin A or cdc2 genes senesced at a population doubling
similar to controls. However, significant extension of life span were seen
in cells that expressed both the transfected human cyclin A and cdc2 genes,
suggesting that these two proteins may be important in controlling the life
span of cells. We investigated the possible role of phosphatases in
senescence. Treatment of quiescent hamster and human fibroblasts with
phosphatase inhibitors (sodium orthovanadate or okadaic acid) allowed cells
to progress from Go/G1 arrest to S-phase. In phosphatase inhibitor-treated
quiescent Syrian hamster embryo fibroblasts, phosphorylation of RB and MAP-
kinase proteins and induction of cdc2 protein accompanied this progression
to DNA synthesis, similar to the effects of serum or mitogen treatment.
Phosphatase inhibitors could also override the block to DNA synthesis in
senescent cells. This suggests that protein phosphatases may play a role
in the negative regulation of cell growth and maintenance of growth arrest.
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ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENES IN CHEMICAL CARCINOGENESIS
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批准号:5202169
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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 C BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:3965229
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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 C BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:3755413
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项目类别:
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资助金额:$0.0万
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负责人:J C BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:3777496
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资助金额:$0.0万
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负责人:J C BARRETT
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依托单位:
CELL SENESCENCE, CARCINOGENESIS, AND AGING
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批准号:3777493
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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 C BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:3841062
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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 C BARRETT
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依托单位:
ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENS IN CHEMICAL CARCINOGENESIS
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批准号:3876903
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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 C BARRETT
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依托单位:
ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENES IN CHEMICAL CARCINOGENESIS
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批准号:3841068
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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 C BARRETT
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依托单位:
CELL SENESCENCE, CARCINOGENESIS, AND AGING
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批准号:3755409
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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 C BARRETT
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依托单位:
ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENES IN CHEMICAL CARCINOGENESIS
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批准号:3777501
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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 C BARRETT
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依托单位:
ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENS IN CHEMICAL CARCINOGENESIS
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批准号:3855891
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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 C BARRETT
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依托单位:
MOLECULAR BASIS FOR CELLULAR CHANGES IN CHEMICAL CARCINOGENESIS
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批准号:4693208
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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 C BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:3918658
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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 C BARRETT
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依托单位:
ROLE OF CELL AND TISSUE STRUCTURE IN NEGATIVE GROWTH REGULATION
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批准号:3855883
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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 C BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:3855885
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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 C BARRETT
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依托单位:
ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENES IN CHEMICAL CARCINOGENESIS
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批准号:3755417
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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 C BARRETT
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依托单位:
CELL SENESCENCE, CARCINOGENESIS, AND AGING
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批准号:2574318
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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 C BARRETT
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依托单位:
ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENS IN CHEMICAL CARCINOGENESIS
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批准号:3941513
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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 C BARRETT
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依托单位:
MOLECULAR BASIS FOR CELLULAR CHANGES IN CHEMICAL CARCINOGENESIS
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批准号:3965236
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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 C BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:5202165
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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 C BARRETT
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依托单位:
海外基金