Cloning and Identification of Genes That Associate with Mammalian Replicative Senescence

Gonos, Efstathios S.; Derventzi, Anastasia; Kveiborg, Marie; Agiostratidou, Georgia; Kassem, Moustapha; Clark, Brian F. C.; Jat, Parmjit; Rattan, Suresh I. S.

doi:10.1006/excr.1998.3948

Cited by 91 publications

(66 citation statements)

References 43 publications

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“…The ratios of incorporation between the cells exposed to repeated stresses or not are very similar to those observed in cells exposed to a single subcytotoxic stress at 450 M H 2 O 2 [16] or to five repeated subcytotoxic stresses at 30 M t-BHP [11]. Using this criteria too, we can suggest that the UVB stressed HDFs behave like presenescent cells.…”

Section: Discussionsupporting

confidence: 68%

“…These three genes, and particularly fibronectin and osteonectin were also found to be expressed in senescent osteoblasts [11], in WI-38 foetal lung HDFs and in IMR-90 foetal lung HDFs. In H 2 O 2 -and t-BHP-induced SIPS of IMR-90 and WI-38 HDFs, these three genes were also found to be overexpressed in similar extents [10].…”

Section: Discussionmentioning

confidence: 89%

“…These genes are also found to be overexpressed when rat fibroblasts immortalized by a temperature permissive SV-40 T antigen are submitted to heat shock, undergo growth arrest, and display a senescence-like morphology [11]. We studied the steady-state mRNA level of these three genes by semi-quantitative RT-PCR in HDFs at late CPDs (>90% of their proliferative life span) and at 72 h after three subcytotoxic stresses at 625 mJ/cm 2 and after five subcytotoxic stresses at 500 mJ/cm 2 (Fig.…”

Section: Gene Expression 72 H After Repeated Subcytotoxic Exposure Tomentioning

confidence: 99%

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UVB-induced premature senescence of human diploid skin fibroblasts

Chainiaux

Magalhães

Eliaers

et al. 2002

The International Journal of Biochemistry & Cell Biology

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In this work, we show that repeated stresses with UVB (290-320 nm) induce stress-induced premature senescence (SIPS) of skin human diploid fibroblasts (HDFs). HDFs at early cumulative population doublings were exposed three or five times to increasing subcytotoxic doses of UVB with one stress per day. After 2 days of recovery, several biomarkers of replicative senescence were established. First, there was an increase in the proportion of cells positive for senescence-associated ␤-galactosidase activity. Second, there was a loss of replicative potential as assessed by a very low level of [ 3 H]-thymidine incorporation. Third, the steady-state level of the mRNA of three senescence-associated genes, i.e. fibronectin, osteonectin and SM22, was increased in HDFs at 72 h after three and five exposures to UVB. In conclusion, these results suggest that it is possible to induce SIPS in HDFs after repeated exposures to subcytotoxic doses of UVB. This model could be used to test whether HDFs in UVB-induced premature senescence are able to promote epithelial cell growth and tumorigenesis in skin, as shown recently with HDFs in H 2 O 2 -induced premature senescence.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 89%

Section: Gene Expression 72 H After Repeated Subcytotoxic Exposure Tomentioning

confidence: 99%

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UVB-induced premature senescence of human diploid skin fibroblasts

Chainiaux

Magalhães

Eliaers

et al. 2002

The International Journal of Biochemistry & Cell Biology

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“…Although identified two decades ago, its functions have not yet been fully elucidated (14,34). Previous reports have correlated clusterin expression with cell responses to stress (35), cell damage recovery (36,37), senescence (38,39), tumorigenesis (14,40), and apoptosis (14). In this report, we have demonstrated that clusterin expression is relatively uniform despite the regional differences of intestinal tumors in average size, frequency, and morphology (9,24).…”

Section: Discussionmentioning

confidence: 53%

Clusterin as a biomarker in murine and human intestinal neoplasia

Chen

Halberg

Ehrhardt

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

109

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Early detection of colorectal cancer is critical for the management of this disease. Biomarkers for early detection of several cancers have been developed and applied clinically in recent years. We have sought to discover candidate biomarkers without the restricted choice of markers placed on microarrays, and without the biological complications of genetic and environmental heterogeneity. We have compared by cDNA subtraction two genetically matched sets of mice, one developing multiple intestinal neoplasia (C57BL͞6J-Apc Min ) and the other tumor-free (C57BL͞6J). One prominent candidate biomarker, clusterin, was then subjected to a series of validation steps. In situ hybridization and immunohistochemistry were used to analyze clusterin expression at a cellular level on a series of murine intestinal and human colonic neoplasms. Elevated clusterin expression was characterized within certain regions of murine and human tumors regardless of tumor stage, location, or mode of initiation. The cells showing high clusterin levels generally lacked differentiation markers and adenomatous polyposis coli antigen. Tumor cells undergoing apoptosis expressed low levels of clusterin. Its specific expression patterns and correlation with cellular events during tumorigenesis make it a useful diagnostic tool in the mouse and a potential contributor to the set of biomarkers for early detection of human colon cancer.

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“…), but most of the studies so far available are still confined to the descriptive level (Rosenberg and Silkensen, 1995). Among these investigations, the evidence for a strong association between clusterin and apoptosis (Pearse et al, 1992), together with the report of its up-regulation in cells surviving death (French et al, 1994;Koch Brandt and Morgans, 1996) and in mammalian senescence Gonos et al, 1998;Marinelli et al, 1994), suggest a possible role for this gene in protecting cells from death (French et al, 1994;Koch Brandt and Morgans, 1996;Miyake et al, 2000;Viard et al, 1999). In a recent work, different forms of clusterin have been immunologically distinguished in apoptotic and death surviving cells (Lakins et al, 1998), suggesting that under the name 'clusterin' a family of different proteins, with different biological significance, are probably still awaiting for a better definition.…”

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confidence: 99%

Clusterin (SGP-2) transient overexpression decreases proliferation rate of SV40-immortalized human prostate epithelial cells by slowing down cell cycle progression

et al. 2002

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Clusterin is a highly conserved, widely distributed glycoprotein whose biological significance is still debated. Involved in many biological processes and disease states, clusterin is induced by cell injury and tissue regression, but is repressed during cell proliferation. We have previously reported that clusterin mRNA induction is associated with epithelial cell atrophy in the rat prostate and both clusterin transcript and protein accumulated in quiescent normal human skin fibroblasts. Here we show that transient clusterin overexpression, in SV40-immortalized human prostate epithelial cells (PNT2), resulted in increased accumulation of cells in the G 0 /G 1 phases of the cell cycle, accompanied by slowdown of cell cycle progression and decrease of DNA synthesis. The activities of ornithine decarboxylase (ODC) and Sadenosylmethionine decarboxylase (AdoMetDC), and the level of histone H3 mRNA (markers of cell proliferation) concomitantly decreased, while Gas1 mRNA (a marker of cell quiescence) accumulated. Thus it appears that clusterin, by opposing the effect of SV40 on the proliferation rate of PNT2 cells, acts as an antioncogene in the prostate, suggesting a role for this gene in controlling proliferation of normal and transformed prostate epithelial cells.

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Cloning and Identification of Genes That Associate with Mammalian Replicative Senescence

Cited by 91 publications

References 43 publications

UVB-induced premature senescence of human diploid skin fibroblasts

UVB-induced premature senescence of human diploid skin fibroblasts

Clusterin as a biomarker in murine and human intestinal neoplasia

Clusterin (SGP-2) transient overexpression decreases proliferation rate of SV40-immortalized human prostate epithelial cells by slowing down cell cycle progression

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