目的分析喉癌肿瘤组织中端粒酶逆转录酶(telomerase reverse transcriptase,TERT)与转录激活蛋白-1(acticator protein 1,AP-1)基因mRNA和蛋白表达水平及两者的相关性。方法利用RT-PCR及量子点标记的免疫荧光染色法,检测24例人喉癌组织...目的分析喉癌肿瘤组织中端粒酶逆转录酶(telomerase reverse transcriptase,TERT)与转录激活蛋白-1(acticator protein 1,AP-1)基因mRNA和蛋白表达水平及两者的相关性。方法利用RT-PCR及量子点标记的免疫荧光染色法,检测24例人喉癌组织中TERT和AP-1的表达。结果在喉癌组织中,TERT与AP-1基因mRNA及蛋白表达水平呈显著正相关,相关系数分别为0.574和0.809,有显著统计学意义(P<0.01)。结论 TERT与AP-1在喉癌组织中的表达具有高度一致性。展开更多
The process of aging is mitigated by the maintenance and repair of chromosome ends(telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the e...The process of aging is mitigated by the maintenance and repair of chromosome ends(telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase(TERT),which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy.Underpinning increased cell proliferation,telomerase is also a key factor in facilitating cancer cell immortalization.The review focuses on aspects of hormonal regulations of telomerase,and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels.In addition,the basic structure and function of two key telomerase enzyme components—the catalytic subunit TERTand the template RNA(TERC)are discussed briefly.展开更多
Estrogen is implicated as playing an important role in aging and tumorigenesis of estrogen responsive tissues;however the mechanisms underlying the mitogenic actions of estrogen are not fully understood.Here we report...Estrogen is implicated as playing an important role in aging and tumorigenesis of estrogen responsive tissues;however the mechanisms underlying the mitogenic actions of estrogen are not fully understood.Here we report that estrogen deficiency in mice caused by targeted disruption of the aromatase gene results in a signi-ficant inhibition of telomerase maintenance of telomeres in mouse ovaries in a tissue-specific manner.The inhibition entails a significant shortening of telomeres and compromised proliferation in the follicular granulosa cell compartment of ovary.Gene expression analysis showed decreased levels of proto-oncogene c-Myc and the telomerase catalytic subunit,telomerase reverse transcriptase(TERT),in response to estrogen deficiency.Estrogen replacement therapy led to increases in TERT gene expression,telomerase activity,telomere length and ovarian tissue growth,thereby reinstating ovary development to normal in four weeks.Our data demonstrate for the first time that telomere maintenance is the primary mechanism mediating the mitogenic effect of estrogen on ovarian granulosa cell proliferation by upregulating the genes of c-Myc and TERT in vivo.Estrogen deficiency or over-activity may cause ovarian tissue aging or tumorigenesis,respectively,through estrogen regulation of telomere remodeling.展开更多
基金supported by grants from the National Health and Medical Research Council of Australia,Cancer Council of Victoria,Australiathe National Basic Research Program of China(Grant No.2012CB911200)a recipient of Monash Postgraduate Scholarship.
文摘The process of aging is mitigated by the maintenance and repair of chromosome ends(telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase(TERT),which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy.Underpinning increased cell proliferation,telomerase is also a key factor in facilitating cancer cell immortalization.The review focuses on aspects of hormonal regulations of telomerase,and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels.In addition,the basic structure and function of two key telomerase enzyme components—the catalytic subunit TERTand the template RNA(TERC)are discussed briefly.
基金This work was supported by grants from the National Health and Medical Research Council of Australia,Australia Research Council,and Cancer Council of Victoria,Australia.S.B.is a recipient of an Australian Postgraduate Award.
文摘Estrogen is implicated as playing an important role in aging and tumorigenesis of estrogen responsive tissues;however the mechanisms underlying the mitogenic actions of estrogen are not fully understood.Here we report that estrogen deficiency in mice caused by targeted disruption of the aromatase gene results in a signi-ficant inhibition of telomerase maintenance of telomeres in mouse ovaries in a tissue-specific manner.The inhibition entails a significant shortening of telomeres and compromised proliferation in the follicular granulosa cell compartment of ovary.Gene expression analysis showed decreased levels of proto-oncogene c-Myc and the telomerase catalytic subunit,telomerase reverse transcriptase(TERT),in response to estrogen deficiency.Estrogen replacement therapy led to increases in TERT gene expression,telomerase activity,telomere length and ovarian tissue growth,thereby reinstating ovary development to normal in four weeks.Our data demonstrate for the first time that telomere maintenance is the primary mechanism mediating the mitogenic effect of estrogen on ovarian granulosa cell proliferation by upregulating the genes of c-Myc and TERT in vivo.Estrogen deficiency or over-activity may cause ovarian tissue aging or tumorigenesis,respectively,through estrogen regulation of telomere remodeling.
