PTEN Up-Regulates the Tumor Metastasis Suppressor Gene <b>
                     <i>Drg-1</i>
                  </b> in Prostate and Breast Cancer

Bandyopadhyay, Sucharita; Pai, Sudha K.; Hirota, Shigeru; Hosobe, Sadahiro; Tsukada, Taisei; Miura, Kouji; Takáno, Yukio; Saito, Ken; Commes, Thérèse; Piquemal, David; Watabe, Misako; Gross, Steven; Wang, Ying; Huggenvik, Jodi I.; Watabe, Kounosuke

doi:10.1158/0008-5472.can-04-1623

Cited by 150 publications

(171 citation statements)

References 21 publications

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“…The ability of chelators to up-regulate the tumor growth and metastasis suppressor Ndrg1 (12)(13)(14) could be vital for their anticancer efficacy. Our results showed that Dp44mT down-regulated these genes in mouse liver (Fig.…”

Section: Discussionmentioning

confidence: 99%

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A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics

Whitnall

Howard²,

Ponka³

et al. 2006

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

468

648

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Novel chemotherapeutics with marked and selective antitumor activity are essential to develop, particularly those that can overcome resistance to established therapies. Iron (Fe) is critical for cell-cycle progression and DNA synthesis and potentially represents a novel molecular target for the design of new anticancer agents. The aim of this study was to evaluate the antitumor activity and Fe chelation efficacy of a new class of Fe chelators using human tumors. In this investigation, the ligands showed broad antitumor activity and could overcome resistance to established antitumor agents. The in vivo efficacy of the most effective chelator identified, di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT), was assessed by using a panel of human xenografts in nude mice. After 7 weeks, net growth of a melanoma xenograft in Dp44mT-treated mice was only 8% of that in mice treated with vehicle. In addition, no differences in these latter animals were found in hematological indices between Dp44mT-treated mice and controls. No marked systemic Fe depletion was observed comparing Dp44mT-and vehicletreated mice, probably because of the very low doses required to induce anticancer activity. Dp44mT caused up-regulation of the Fe-responsive tumor growth and metastasis suppressor Ndrg1 in the tumor but not in the liver, indicating a potential mechanism of selective anticancer activity. These results indicate that the novel Fe chelators have potent and broad antitumor activity and can overcome resistance to established chemotherapeutics because of their unique mechanism of action.cancer ͉ di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone ͉ Ndrg1

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Section: Discussionmentioning

confidence: 99%

“…Moreover, in cultured cells Dp44mT resulted in marked up-regulation of the Fe-responsive tumor growth and metastasis suppressor Ndrg1 (N-myc downstream regulated gene-1) (12). Up-regulation of Ndrg1 suppresses primary tumor growth and metastasis (13,14) and may be another mechanism by which chelators inhibit cancer cell proliferation.…”

mentioning

confidence: 99%

A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics

Whitnall

Howard²,

Ponka³

et al. 2006

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

468

648

View full text Add to dashboard Cite

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“…The traditional view of metastasis includes the process of clonal selection in which rare variant clones within the primary tumor become capable of completing the complex multistep metastatic process (Fidler, 2003;Talmadge, 2007). Recently, expression profiling analyses have revealed various tumor metastasis genes and metastasis suppressor genes, which not only regulate the metastatic process (Dong et al, 1995(Dong et al, , 1996Bandyopadhyay et al, 2004;Nuyten and van de Vijver, 2006;Rinker-Schaeffer et al, 2006;Tomida et al, 2007;Albini et al, 2008;Kim et al, 2009;Lukes et al, 2009) but also maintain the microenvironment of tumor cells, and initiate the process of epithelial-mesenchymal transition (EMT).…”

Section: Introductionmentioning

confidence: 99%

The microRNA network and tumor metastasis

2009

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Metastasis is the most significant process affecting the clinical management of cancer patients and occurs in multiple sequential steps. However, the molecular pathways underlying each step still remain obscure. Recent research has shown that there is a microRNA (miRNA) network that functions as a regulator of tumor metastasis. In this paper, we review the role of miRNAs in tumor metastasis, including control of epithelial-mesenchymal transition, regulation of metastasis-associated genes and epigenetic alterations. More information on miRNAs will promote a better understanding of the molecular mechanism of metastasis.

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“…The significant inverse correlation of NDRG1 expression with the extent of metastasis in a clinical setting raised an important question as to whether the down-regulation of NDRG1 is cause or result of metastases. To address this issue, we overexpressed the NDRG1 gene in a highly metastatic prostate cell line AT6.1 and implanted it into severe combined immunodeficiency mice (33). Our results indicate that NDRG1 has the ability to suppress the metastatic process of prostate cancer cells without affecting tumorigenicity in vivo.…”

mentioning

confidence: 98%

KAI1 Gene Is Engaged in NDRG1 Gene-mediated Metastasis Suppression through the ATF3-NFκB Complex in Human Prostate Cancer

Iiizumi‐Gairani

Okuda

et al. 2011

Journal of Biological Chemistry

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PTEN Up-Regulates the Tumor Metastasis Suppressor Gene Drg-1 in Prostate and Breast Cancer

Cited by 150 publications

References 21 publications

A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics

A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics

The microRNA network and tumor metastasis

KAI1 Gene Is Engaged in NDRG1 Gene-mediated Metastasis Suppression through the ATF3-NFκB Complex in Human Prostate Cancer

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