Inhibition of PAX2 expression results in alternate cell death pathways in prostate cancer cells differing in p53 status

Gibson, Willietta; Green, Ashley; Bullard, Rebecca S.; Eaddy, Andre C.; Donald, Carlton D.

doi:10.1016/j.canlet.2006.08.007

Cited by 20 publications

(24 citation statements)

References 32 publications

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“…1D). It was reported that inhibition of PAX2 led to cancer cell apoptosis (3,10). However, in our work, knockdown of PAX2 did not significantly induce apoptosis of RKO cells (supplemental Fig.…”

Section: Discussioncontrasting

confidence: 53%

“…1D). A few studies showed that PAX2 inhibition resulted in apoptosis of cancer cells (3,10). We examined RKO cells and found that, under our experimental conditions, knockdown of PAX2 did not significantly induce cell apoptosis (supplemental Fig.…”

Section: Pax2 Promotes Proliferation and Xenograft Growth Of Colonmentioning

confidence: 81%

“…Similarly, inhibition of PAX2 in Kaposi sarcoma cells led to cell death and reduced cell motility and invasiveness when challenged by serum deprivation or vincristine treatment (9). PAX2 inhibition also resulted in cell death of prostate cancer cells (10). Although a number of studies have demonstrated that PAX2 plays an important role in cancer, the underlying mechanisms are not well understood.…”

mentioning

confidence: 99%

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PAX2 Protein Induces Expression of Cyclin D1 through Activating AP-1 Protein and Promotes Proliferation of Colon Cancer Cells

Zhang

Yan

et al. 2012

Journal of Biological Chemistry

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Background: PAX2, a transcription factor, plays a role in embryogenesis. Results: Knockdown of PAX2 inhibits colon cancer cells proliferation and xenograft growth. PAX2 activates AP-1, leading to increased expression of cyclin D1. Conclusion: PAX2 promotes proliferation of colon cancer cells via AP-1. Significance: PAX2 exhibits oncogenic properties in colon cancer cells and may serve as a target for cancer therapy.

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Section: Discussioncontrasting

confidence: 53%

Section: Pax2 Promotes Proliferation and Xenograft Growth Of Colonmentioning

confidence: 81%

mentioning

confidence: 99%

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PAX2 Protein Induces Expression of Cyclin D1 through Activating AP-1 Protein and Promotes Proliferation of Colon Cancer Cells

Zhang

Yan

et al. 2012

Journal of Biological Chemistry

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“…5). The cytotoxic effect of downregulating PAX2 gene expression is in agreement with other studies demonstrating a potent antiapoptotic function of PAX proteins in melanoma, ovarian, bladder and prostate carcinoma cell lines (13,23,24). In silico analysis of the Oncomine registry confirmed that PAX2 expression is elevated in medulloblastoma compared to normal cerebellum ( Fig.…”

Section: Discussionsupporting

confidence: 90%

PAX2 is an antiapoptotic molecule with deregulated expression in medulloblastoma

et al. 2012

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Abstract. PAX2 is a paired box transcription factor possessing a fundamental role in the embryogenesis of hindbrain and urinary tract. PAX genes are proto-oncogenes, PAX2 expression may contribute to the pathogenesis of renal cell carcinoma. Because of the expression of PAX2 in the developing hindbrain and its essential role in cerebellar development, it has been hypothesized that PAX2 may also be involved in medulloblastoma tumorigenesis. We investigated the expression pattern of PAX2 and various genes of the neuronal lineage in medulloblastoma and glioma cell lines. We found high expression of PAX2 mRNA and PAX2 protein in medulloblastoma cells and some glioma cell lines independent of their neuronal lineage gene expression signature. Gene suppression of PAX2 decreased the expression of the PAX2 transcriptional target GDNF in Daoy cells and had a profound cytotoxic effect in vitro on Daoy medulloblastoma and T98G glioma cells. Expression of PAX2 was then assessed in two separate medulloblastoma tissue microarrays with a total of 61 patient samples by immunohistochemistry. PAX2 expression was detected in the majority of medulloblastoma samples and correlated with less differentiated histology. Therefore, PAX2 is a biomarker for a more aggressive medulloblastoma phenotype and may represent a novel therapeutic target.

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“…SiRNA knock-down and verification was performed as previously described (Gibson, et al, 2007). Briefly, a pool of four complementary siRNAs targeting human PAX2 mRNA (Accession No.…”

Section: Sirna Silencing Of Pax2mentioning

confidence: 99%

Functional analysis of the host defense peptide Human Beta Defensin-1: New insight into its potential role in cancer

Bullard

Gibson

Bose

et al. 2008

Molecular Immunology

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Although it is known that innate immunity is key for protecting the body against foreign agents such as bacteria, little is known about elements of the innate immune system that have anti-tumor activity. Human Beta Defensin-1 (hBD-1), an important component of the innate immune response, is lost at high frequencies in malignant prostatic tissue, while high levels of expression are maintained in adjacent benign regions. In prostate carcinoma, frequent genetic alterations occur in the 8p22-23 region and several studies indicate there may be multiple tumor suppressor genes present within this region. The high incidence of loss of hBD-1 expression in prostate cancer, along with its chromosomal location of 8p23.2, raised the possibility that it may play a role in tumor suppression. To gain insight as to its function in prostate cancer, hBD-1 was cloned and ectopically expressed in four prostate cancer cell lines. Induction of hBD-1 expression resulted in a decrease in cellular growth in DU145 and PC3 cells. However, hBD-1 has no effect on the growth of androgen receptor (AR) positive LNCaP prostate cancer cells, but was again growth suppressive to PC3 cells with ectopic AR expression (PC3/AR+). hBD-1 also caused rapid induction of cytolysis and caspase-mediated apoptosis in DU145 and PC3 prostate cancer cells. Although the regulation of hBD-1 was not addressed in this study, our preliminary data demonstrated that the pathways involoved may include cMYC and/or PAX2. Data presented here are the first to provide evidence of its potential role in prostate cancer cell death.

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Inhibition of PAX2 expression results in alternate cell death pathways in prostate cancer cells differing in p53 status

Cited by 20 publications

References 32 publications

PAX2 Protein Induces Expression of Cyclin D1 through Activating AP-1 Protein and Promotes Proliferation of Colon Cancer Cells

PAX2 Protein Induces Expression of Cyclin D1 through Activating AP-1 Protein and Promotes Proliferation of Colon Cancer Cells

PAX2 is an antiapoptotic molecule with deregulated expression in medulloblastoma

Functional analysis of the host defense peptide Human Beta Defensin-1: New insight into its potential role in cancer

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