Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.

Shaw, Phillip; Bovey, R; Tardy, Sébastien; Sahli, Roland; Sordat, Bernard; Costa, Judite

doi:10.1073/pnas.89.10.4495

Cited by 742 publications

(405 citation statements)

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“…The overexpression of p53 protein that is observed in irradiated cells can also be produced by ectopic p53 expression after p53 gene transfer into non irradiated control cells. Non irradiated cells expressing thereby high levels of wildtype p53 have been shown to undergo either cell cycle arrest in G1 (Diller et al, 1990;Lin et al, 1992) or apoptosis (Yonish-Rouach et al, 1991, 1994Shaw et al, 1992).…”

Section: Amino-terminal Region Of P53mentioning

confidence: 99%

Twenty years of p53 research: structural and functional aspects of the p53 protein

1999

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Section: Amino-terminal Region Of P53mentioning

confidence: 99%

Twenty years of p53 research: structural and functional aspects of the p53 protein

1999

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“…Its increased expression is also necessary for induction of apoptosis in other tissues (YonishRouach et al, 1991;Shaw et al, 1992;Ryan et al, 1993). Our data have demonstrated that an increase in p53 protein expression preceeded the occurrence of apoptosis in vivo.…”

Section: Discussionmentioning

confidence: 99%

Comparative alterations in p53 expression and apoptosis in the irradiated rat small and large intestine

Arai

Kida²,

Harmon³

et al. 1996

Br J Cancer

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Summary Temporal and spatial relationships between radiation-induced apoptosis and expression of p53 mRNA and protein were compared in rat small and large intestine. Apoptosis was quantified using morphological criteria, and p53 expression determined by immunohistochemistry or whole-tissue Northern analysis. In the small intestine, peak levels of apoptosis appeared earlier (4 h) than in the large intestine (6 h). p53 mRNA transcript levels in small and large intestine were not significantly altered from control levels at any time after treatment. However, in treated small and large intestine, cells showed increased positivity for p53 protein, increasing 10-fold over control levels 4-5 h after irradiation. A strong spatial relationship was found between high incidence apoptosis and p53 protein positivity. We compared published data of stem cell population positions for small and large intestine with our results. Target cells for apoptosis and p53 expression occurred at approximately fifth position from the crypt base of the small intestine, a zone coincident with stem cell population. Target cell position for apoptosis and p53 expression in the large intestine was again at fifth or sixth position from the base, but this zone is not the reported stem cell position (first or second position) for large intestine. Results from our model of radiation-induced intestinal apoptosis indicate that p53 protein is closely associated both temporally and spatially with the induction of apoptosis, and support the work of others in suggesting that p53 expression is modulated post-transcriptionally. Furthermore, our results support a hypothesis that apoptotic targeting of damaged stem cell populations, early response for apoptotic removal of DNA-damaged cells and/or early repair of these damage cells are all important parameters that determine differences in levels of tumorigenesis in the small and large intestine.

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“…Touchdown PCR was carried out. An initial denaturation at 95 1C for 10 min was followed by 5 JEG-3 and JAR cultures were transfected with the ASPP1 construct (a generous gift from Professor Xin Lu) using Lipofectamine 2000 (Invitrogen). The pCDNA 3.1 vector was used as a control.…”

Section: Dna Preparation Sodium Bisulfite Modification and Ms-pcrmentioning

confidence: 99%

“…Moreover, hydatidiform moles with lower apoptotic activity are associated with the development of gestational trophoblastic neoplasm. 3,4 The tumor-suppressor protein p53 is an important inducer of apoptosis, 5 and overexpression of wildtype p53 has been demonstrated in hydatidiform moles and choriocarcinomas when compared with normal placentas. [6][7][8][9] Unlike most other solid tumors, direct cDNA sequencing could not detect any mutation in the overexpressed p53 in gestational trophoblastic disease.…”

mentioning

confidence: 99%

Downregulation of ASPP1 in gestational trophoblastic disease: correlation with hypermethylation, apoptotic activity and clinical outcome

et al. 2011

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Gestational trophoblastic disease encompasses a spectrum of trophoblastic lesions including true neoplasms such as choriocarcinomas and the potentially malignant hydatidiform moles, which may develop persistent disease requiring chemotherapy. ASPP1, a member of apoptosis-stimulating proteins of p53 (ASPPs), is a proapoptotic protein that can stimulate apoptosis through its interaction with p53. We evaluated the promoter methylation and expression profiles of ASPP1 in different trophoblastic tissues and its in vitro functional effect on two choriocarcinoma cell lines, namely JEG-3 and JAR. Significant downregulation of ASPP1 mRNA and protein levels was demonstrated in hydatidiform moles and choriocarcinomas, when compared with normal placentas by quantitative-PCR and immunohistochemistry. The ASPP1 mRNA level was significantly correlated with its hypermethylation status, evaluated with methylation-specific PCR, in placenta and gestational trophoblastic disease samples (P ¼ 0.024). Moreover, lower ASPP1 immunoreactivity was shown in hydatidiform moles that progressed to persistent gestational trophoblastic neoplasms than in those that regressed (P ¼ 0.045). A significant correlation was also found between expression of ASPP1 and proliferative indices (assessed by Ki67 and MCM7), apoptotic activity (M30 CytoDeath antibody), p53 and caspase-8 immunoreactivities. An in vitro study showed that ectopic expression of ASPP1 could trigger apoptosis through intrinsic and extrinsic pathways as indicated by an increase in cleaved caspase-9 and Fas ligand protein expression. The latter suggests a hitherto unreported novel link between ASPP1 and the extrinsic pathway of apoptosis. Our findings suggest that downregulation of ASPP1 by hypermethylation may be involved in the pathogenesis and progress of gestational trophoblastic disease, probably through its effect on apoptosis.

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Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.

Cited by 742 publications

References 44 publications

Twenty years of p53 research: structural and functional aspects of the p53 protein

Twenty years of p53 research: structural and functional aspects of the p53 protein

Comparative alterations in p53 expression and apoptosis in the irradiated rat small and large intestine

Downregulation of ASPP1 in gestational trophoblastic disease: correlation with hypermethylation, apoptotic activity and clinical outcome

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