Multiple pathways control cell growth and transformation: overlapping and independent activities of p53 and p21Cip1/WAF1/Sdi1

Cox, Lynne S.

doi:10.1002/(sici)1096-9896(199710)183:2<134::aid-path960>3.0.co;2-d

Cited by 111 publications

(77 citation statements)

References 54 publications

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“…Additionally, the dysfunction of p53, a transcription factor known as a tumor suppressor, has been associated with poor clinical outcome for patients with CLL (22). The cyclin dependent kinase inhibitor, p21 cip1 , is known to be a transcriptional target of p53 (23). With the possibility that the mechanism relating ZAP-70 levels and prognosis may involve the p53 pathway, we looked for correlations of ZAP-70, phospho-ZAP-70, and phosphoSyk with p21 cip1 .…”

Section: Correlation Of Phospho-syk and P21 Cip1 Expression In Leukemmentioning

confidence: 99%

Correlation between ZAP‐70, phospho‐ZAP‐70, and phospho‐Syk expression in leukemic cells from patients with CLL

Kaplan

Meyerson

et al. 2009

Cytometry Part B Clinical

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Section: Correlation Of Phospho-syk and P21 Cip1 Expression In Leukemmentioning

confidence: 99%

Correlation between ZAP‐70, phospho‐ZAP‐70, and phospho‐Syk expression in leukemic cells from patients with CLL

Kaplan

Meyerson

et al. 2009

Cytometry Part B Clinical

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“…Cell death was greatest in MT1A2 and A549 cells transduced with Ad vectors expressing p16, p18 and p27 ( Figure 2 and Table 2), whereas p19 and p21 expression had a more cytostatic e ect on cell proliferation. The e ects of Ad vector driven p53 expression were also examined since its growth inhibitory properties have been well characterized and since p53-expressing Ads have been shown to inhibit DNA synthesis and promote apoptosis (Bacchetti and Graham, 1993;Cox, 1997;Putzer et al, 1998). Interestingly, while infection with Adp53wt had an antiproliferative e ect in A549 cells, which is most likely due to induction of endogenous p21 expression (Figure 1b), in mouse MT1A2 cells the e ects of human p53 over-expression were more modest.…”

Section: Inhibition Of Tumour Cell Growth By Exogenous Ckis In Vitromentioning

confidence: 99%

Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21WAF1/CIP1 and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity

et al. 1999

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Cell cycle regulatory proteins are important candidates for therapeutic tumour suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16 INK4A , p18 INK4C , p19 INK4D , p21 WAF1/CIP1 and p27 KIP1 under the control of the murine cytomegalovirus immediate early gene promoter. These vectors directed the e cient expression of each of the cyclin kinase inhibitors and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing functional pRb. In pRbde®cient cells, expression of the cyclin kinase inhibitors was not e ective in inhibiting DNA replication or growth arrest. Interestingly, three of the cyclin kinase inhibitors, p16, p18 and p27 were found to induce apoptotic death in transduced HeLa and A549 cells. When the vectors were tested for their ability to inhibit tumorigenicity in a polyomavirus middle T antigen model of murine breast carcinoma, expression of the cyclin kinase inhibitors resulted in a delay in tumour formation that varied from several weeks for the p19 expressing vector to greater than 25 weeks for the p27 expressing vector. When tumours were injected directly with the adenovirus vectors expressing the cyclin kinase inhibitors, only treatment with the vector expressing p16 resulted in a delay in tumour growth.

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“…Activation of programmed cell death may be related to several initiating events, such as the synthesis of the most important tumor suppressor p53, a protein whose gene is often mutated in GBMs (38,39). Furthermore, we observed a decrease in the expressions of the anti-apoptotic Bcl-2 and increase in the proapoptotic BAD genes (39,40).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists

Jászberényi

Rick

Popovics

et al. 2013

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

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The dismal prognosis of malignant brain tumors drives the development of new treatment modalities. In view of the multiple activities of growth hormone-releasing hormone (GHRH), we hypothesized that pretreatment with a GHRH agonist, JI-34, might increase the susceptibility of U-87 MG glioblastoma multiforme (GBM) cells to subsequent treatment with the cytotoxic drug, doxorubicin (DOX). This concept was corroborated by our findings, in vivo, showing that the combination of the GHRH agonist, JI-34, and DOX inhibited the growth of GBM tumors, transplanted into nude mice, more than DOX alone. In vitro, the pretreatment of GBM cells with JI-34 potentiated inhibitory effects of DOX on cell proliferation, diminished cell size and viability, and promoted apoptotic processes, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide proliferation assay, ApoLive-Glo multiplex assay, and cell volumetric assay. Proteomic studies further revealed that the pretreatment with GHRH agonist evoked differentiation decreasing the expression of the neuroectodermal stem cell antigen, nestin, and up-regulating the glial maturation marker, GFAP. The GHRH agonist also reduced the release of humoral regulators of glial growth, such as FGF basic and TGFβ. Proteomic and geneexpression (RT-PCR) studies confirmed the strong proapoptotic activity (increase in p53, decrease in v-myc and Bcl-2) and antiinvasive potential (decrease in integrin α3) of the combination of GHRH agonist and DOX. These findings indicate that the GHRH agonists can potentiate the anticancer activity of the traditional chemotherapeutic drug, DOX, by multiple mechanisms including the induction of differentiation of cancer cells.peptide analogs | targeted therapy

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Multiple pathways control cell growth and transformation: overlapping and independent activities of p53 and p21Cip1/WAF1/Sdi1

Cited by 111 publications

References 54 publications

Correlation between ZAP‐70, phospho‐ZAP‐70, and phospho‐Syk expression in leukemic cells from patients with CLL

Correlation between ZAP‐70, phospho‐ZAP‐70, and phospho‐Syk expression in leukemic cells from patients with CLL

Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21WAF1/CIP1 and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity

Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists

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