Transfection of melanoma cells with antisense<i>PAX3</i>oligonucleotides additively complements cisplatin-induced cytotoxicity

He, Shan; Stevens, G. H. J.; Braithwaite, Antony W.; Eccles, Michael R.

doi:10.1158/1535-7163.mct-04-0252

Cited by 49 publications

(55 citation statements)

References 27 publications

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“…Accordingly, suppression of Pax2, Pax7 or Pax3 in tumour cell lines has been shown to increase cell death (Margue et al, 2000;Muratovska et al, 2003;He et al, 2005), indicating that high expression levels of pax genes are most likely essential for evading the apoptotic programme, a hallmark of cancer (Hanahan and Weinberg, 2000). Interestingly, deletion of two Pax2/5/ 8-related genes (egl-38 and pax2) in Caenorhabditis elegans was shown to induce apoptosis in somatic and germline cells via the antiapoptotic gene bcl-2 (Park et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

The transcription factor PAX4 acts as a survival gene in INS-1E insulinoma cells

Brun¹,

Duhamel²,

He³

et al. 2007

Oncogene

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The paired/homeodomain transcription factor Pax4 is essential for islet b-cell generation during pancreas development and their survival in adulthood. High Pax4 expression was reported in human insulinomas indicating that deregulation of the gene may be associated with tumorigenesis. We report that rat insulinoma INS-1E cells express 25-fold higher Pax4 mRNA levels than rat islets. In contrast to primary b-cells, activin A but not betacellulin or glucose induced Pax4 mRNA levels indicating dissociation of Pax4 expression from insulinoma cell proliferation. Short hairpin RNA adenoviral constructs targeted to the paired domain or homeodomain (viPax4PD and viPax4HD) were generated. Pax4 mRNA levels were lowered by 73 and 50% in cells expressing either viPax4PD or viPax4HD. Transcript levels of the Pax4 target gene bcl-xl were reduced by 53 and 47%, whereas Pax6 and Pdx1 mRNA levels were unchanged. viPax4PD-infected cells displayed a twofold increase in spontaneous apoptosis and were more susceptible to cytokine-induced cell death. In contrast, proliferation was unaltered. RNA interference-mediated repression of insulin had no adverse effects on either Pax4 or Pdx1 expression as well as on cell replication or apoptosis. These results indicate that Pax4 is redundant for proliferation of insulinoma cells, whereas it is essential for survival through upregulation of the antiapoptotic gene bcl-xl.

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Section: Discussionmentioning

confidence: 99%

The transcription factor PAX4 acts as a survival gene in INS-1E insulinoma cells

Brun¹,

Duhamel²,

He³

et al. 2007

Oncogene

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“…The role of PAX3 and its isoforms in myogenesis, melanogenesis, neurogenesis, and related oncogenesis have been well established ( Figure 1). PAX3 is specifically detected in most neural crest-derived Ewing's family tumors and in most peripheral neuroectodermal tumors [34], small cell lung cancer [18], and most primary cultured melanomas [18,34,79]. Screening of Ewing's sarcoma and peripheral neuroectodermal tumor specimens and its derived cell lines showed elevated PAX3 expression [34].…”

Section: Pax3 Plays An Oncogenic Role In Various Types Of Tumorsmentioning

confidence: 99%

“…PAX3 is a key transcription factor in regulating the expression of a variety of melanocytic genes [22,83]. Inhibiting the expression of PAX3 using antisense RNA in melanoma cell lines resulted in dose dependent reduction of proliferation of melanoma cells and induction of apoptosis, suggesting role for PAX3 in melanoma cell survival [78,79]. Pax3 reduction also induces a loss of melanogenesis in melanoma cells, followed by a sharp decrease in MITF mRNA and gene promoter activity.…”

Section: Rhabdomyosarcomamentioning

confidence: 99%

PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

Arasu

Murugan

Essa

et al. 2018

BioMed Research International

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Metastasis is the most deadly aspect of cancer and results from acquired gene regulation abnormalities in tumor cells. Transcriptional regulation is an essential component of controlling of gene function and its failure could contribute to tumor progression and metastasis. During cancer progression, deregulation of oncogenic or tumor suppressive transcription factors, as well as master cell fate regulators, collectively influences multiple steps of the metastasis cascade, including local invasion and dissemination of the tumor to distant organs. Transcription factor PAX3/Pax3, which contributes to diverse cell lineages during embryonic development, plays a major role in tumorigenesis. Mutations in this gene can cause neurodevelopmental disease and the existing literature supports that there is a potential link between aberrant expression of PAX3 genes in adult tissues and a wide variety of cancers. PAX3 function is tissue-specific and could contribute to tumorigenesis either directly as oncogene or as a tumor suppressor by losing its function. In this review, we discuss comprehensively the differential role played by PAX3 in various tissues and how its aberrant expression is implicated in disease development. This review particularly highlights the oncogenic and tumor suppressor role played by PAX3 in different cancers and underlines the importance of precisely identifying tissue-specific role of PAX3 in order to determine its exact role in development of cancer.

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“…153,160 Recent studies demonstrate that Pax3 enhances the rate of p53 degradation. Pax3 can down-regulate a p53 mutant incapable of binding MDM2, 161 thereby implicating Pax3 in the regulation of other negative regulators of p53 stability (e.g., PirH2 or Cop1).…”

Section: Contribution Of P53 To Cns Pathologymentioning

confidence: 99%

p53 in the CNS: Perspectives on Development, Stem Cells, and Cancer

2011

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The p53 tumor suppressor potently limits the growth of immature and mature neurons under conditions of cellular stress. Although loss of p53 function contributes to the pathogenesis of central nervous system (CNS) tumors, excessive p53 function is implicated in neural tube defects, embryonic lethality, and neuronal degeneration. Thus, p53 function must be tightly controlled. The anti-proliferative properties of p53 are mediated, in part, through the induction of apoptosis, cell cycle arrest, and senescence. Although there is still much to be learned about the role of p53 in these processes, recent evidence supports exciting new roles for p53 in a wide range of processes, including neural precursor cell self-renewal, differentiation, and cell fate decisions. Understanding the full repertoire of p53 function in CNS development and tumorigenesis may provide us with novel points of therapeutic intervention for human diseases of the CNS.

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Transfection of melanoma cells with antisensePAX3oligonucleotides additively complements cisplatin-induced cytotoxicity

Cited by 49 publications

References 27 publications

The transcription factor PAX4 acts as a survival gene in INS-1E insulinoma cells

The transcription factor PAX4 acts as a survival gene in INS-1E insulinoma cells

PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

p53 in the CNS: Perspectives on Development, Stem Cells, and Cancer

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