p53 expression overcomes p21WAF1/CIP1-mediated G1 arrest and induces apoptosis in human cancer cells

Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hizuta, Akio; Yasuda, Tatsuji; Zhang, Wei Wei; Roth, Jack A.; Tanaka, Noriaki

doi:10.1038/sj.onc.1201362

Cited by 87 publications

(59 citation statements)

References 14 publications

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“…These ®ndings suggest that multiple pathways leading to apoptosis, including CD95-dependent and CD95-independent mechanisms, could be initiated by an ectopic p53 gene transfer. We previously demonstrated that p53 overexpression can be a powerful inducer of apoptosis even in cell cycle-arrested tumor cells (Kagawa et al, 1997). These results, taken together, indicate that the wt-p53 gene transfer may be potentially useful for gene-based anticancer therapy.…”

Section: Discussionmentioning

confidence: 79%

“…Numerous studies have shown that p53 protein activates the transcription of a number of genes such as p21 waf1/cip1 (Harper et al, 1993;Xiong et al, 1993;El-Deiry et al, 1993), bax (Selvakumaran et al, 1994;Miyashita and Reed, 1995), mdm2 (Momand et al, 1992), insulin-like growth factor-binding protein (IGF-BP) (Buckbinder et al, 1995) and CD95 (Fas/ APO-1) (Owen-Schaub et al, 1995). We previously reported that the overexpression of the wild-type p53 (wt-p53) gene by recombinant, replication-de®cient viral vectors induced apoptosis in a variety of human cancer cells di ering their p53 status (Fujiwara et al, 1993;Kagawa et al, 1997). The elucidation of the molecular mechanism of p53-mediated apoptosis would provide insights into the mode of action of DNAdamaging conventional cancer therapies, including chemotherapeutic agents and ionizing radiation, as well as the development of novel cancer gene therapies using the wt-p53 gene.…”

Section: Introductionmentioning

confidence: 99%

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Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells

et al. 1999

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The CD95 (Fas/APO-1) system regulates a number of physiological and pathological processes of cell death. The ligand for CD95 induces apoptosis in sensitive target cells by interacting with a transmembrane cell surface CD95 receptor. We previously reported that the recombinant adenovirus-mediated transfer of the wildtype p53 gene caused apoptotic cell death in a variety of human cancer cells. To better understand the mechanism responsible for this cell death signaling, we have investigated the potential involvement of the CD95 receptor/ligand system in p53-mediated apoptosis. The transient expression of the wild-type p53 gene upregulated the CD95 ligand mRNA as well as protein expression in H1299 human lung cancer cells de®cient for p53 and in DLD-1 and SW620 human colon cancer cells with mutated p53, all of which constitutively expressed CD95 receptor as shown by a¯ow cytometric analysis, and induced rapid apoptotic cell death as early as 24 h after gene transfer. However, the sensitivity to the cytolytic e ect of agonistic anti-CD95 antibody (CH11) varied among these cell lines: CH11 induced apoptosis in H1299 cells, but not in DLD-1 and SW620 cells despite their abundant CD95 receptor expression, suggesting that the CD95 receptors on DLD-1 and SW620 cells might be inactivated. In addition, an antagonistic anti-CD95 ligand antibody (4H9) that interfered with the CD95-receptor-ligand interaction partially reduced the apoptosis induced by the wild-type p53 gene transfer in H1299 cells, whereas apoptosis of DLD-1 and SW620 cells occurred in the presence of 4H9. Taken together, these ®ndings led us to conclude that the CD95 receptor/ligand system is di erentially involved in p53-mediated apoptosis, suggesting that the restoration of the wild-type p53 function may mediate apoptosis through CD95 receptor/ligand interactions as well as an alternative pathway.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells

et al. 1999

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“…Examples of such viral proteins are the E1B protein of adenovirus, the E6 protein of human papilloma virus, and the large T antigen of SV 40 virus. It has also been proposed that the level of p53 may determine whether growth arrest (low levels) or apoptosis (high levels) pathways are induced (Kagawa et al, 1997;WroneSmith et al, 1999;Zhao et al, 2000b;Pyrzynska et al, 2002). These findings hint at the need for higher levels of p53 in order to transactivate pro-apoptotic genes.…”

Section: Apoptosis Versus Necrosismentioning

confidence: 99%

Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines

Holmes¹,

Soprano²,

Soprano³

2004

Journal Cellular Physiology

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Apoptosis is also known as programmed cell death. Apoptosis plays an essential role in maintaining normal tissue and cell physiology in multicellular organisms. Clearance of aberrant or pre-cancerous cells occurs through the induction of apoptosis. It has been reported that many tumors and tumor cell lines have dysfunctional apoptosis signaling, causing these tumors to escape immune monitoring and internal cellular control mechanisms. One potential cause of this dysfunctional apoptosis is the tumor suppressor p53, an important regulator of growth arrest and apoptosis that is mutated in over 50% of all cancers. Retinoids have great potential in the areas of cancer therapy and chemoprevention. While some tumor cells are sensitive to the growth inhibitory effects of natural retinoids such as all-trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-[3-(1-Admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and fenretinide N-[4-hydroxyphenyl] retinamide (4-HPR) are conformationally restricted synthetic retinoids that induce growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines. Recently, we have identified the molecular pathways of apoptosis induced by treatment of ovarian carcinoma cells with mutated p53 by CD437 and 4-HPR.

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“…21,22 Reintroduction of wild-type p53 (wt-p53) into tumor cells has led to a variety of effects, including growth arrest and apoptosis. [23][24][25] Although some tumor cell types, such as uterine carcinoma or head and neck carcinoma cells, unequivocally show p53-induced apoptosis induction, the results obtained for most of tumor cell types are controversial. 6,26 -29 These contradictory results illustrate that the outcome of wt-p53 gene replacement is not a predictable event but rather depends upon the cell system in which p53 is re-expressed.…”

mentioning

confidence: 99%

Modulation of drug cytotoxicity by reintroduction of wild-type p53 gene (Ad5CMV-p53) in human pancreatic cancer

et al. 2000

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Chemotherapy does not significantly improve prognosis in pancreatic cancer. New therapeutical approaches involving p53 gene replacement appear to be very encouraging due to the key role of p53 in the cell response to DNA damage. Here, we have evaluated the effectiveness of combining wild-type p53 (wt-p53) gene reintroduction (Ad5CMV-p53) and exposure to two genotoxic drugs, gemcitabine and cisplatin, in several human pancreatic cell lines. The efficiency of the combinations was clearly dependent upon timing, as assessed by cell survival determinations. Although wt-p53 transduction before drug treatment induced chemoresistance, p53 transduction in cells treated previously with gemcitabine increased cytotoxicity. Cell cycle profiles showed significant decreases in the percentage of cells in the S phase as a consequence of arrests provoked by the expression of exogenous p53, reducing the number of cells susceptible to the drug. The sensitivity of cells to cisplatin, which has a lower degree of S-phase specificity, was not modified as much by p53 gene replacement. In contrast, the recognition of the previous drug-induced DNA damage by the newly expressed wt-p53 elicited increases in sub-G 1 populations, consistent with the annexin determinations and bax/bcl-2 ratios observed. Experiments on subcutaneous pancreatic xenografts corroborated the effectiveness of this approach in vivo. Thus, the combination of p53 transduction and chemotherapy, under a correct schedule of administration, appears to be a very promising therapy for human pancreatic cancer. Cancer Gene Therapy (2000) 7, 545-556

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p53 expression overcomes p21WAF1/CIP1-mediated G1 arrest and induces apoptosis in human cancer cells

Cited by 87 publications

References 14 publications

Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells

Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells

Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines

Modulation of drug cytotoxicity by reintroduction of wild-type p53 gene (Ad5CMV-p53) in human pancreatic cancer

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