Amplification, up‐regulation and over‐expression of <i>DVL‐1</i>, the human counterpart of the <i>Drosophila disheveled</i> gene, in primary breast cancers

Nagahata, Takemitsu; Shimada, Takashi; Harada, Akima; Nagai, Hisaki; Onda, Masamitsu; Yokoyama, Shiro; Shiba, Tadayoshi; Jin, Enjing; Kawanami, Oichi; Emi, Mitsuru

doi:10.1111/j.1349-7006.2003.tb01475.x

Cited by 112 publications

(89 citation statements)

References 23 publications

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“…Although Wnt/β-catenin pathway mutations are rarely detected in breast tumors, elevated levels of nuclear and/or cytoplasmic β-catenin are frequently found and are associated with poor prognosis (40). Furthermore, DVL1 is up-regulated in 50% of human breast cancers, and phosphorylated DVL proteins have been detected in many breast tumor cell lines (41,42).…”

Section: Discussionmentioning

confidence: 99%

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Wang

Zhou

et al. 2016

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

162

119

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Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited promising anticancer activity; however, the molecular mechanisms of action of prodigiosin on malignant cells remain unclear. Aberrant activation of the Wnt/β-catenin signaling cascade is associated with numerous human cancers. In this study, we identified prodigiosin as a potent inhibitor of the Wnt/ β-catenin pathway. Prodigiosin blocked Wnt/β-catenin signaling by targeting multiple sites of this pathway, including the lowdensity lipoprotein-receptor-related protein (LRP) 6, Dishevelled (DVL), and glycogen synthase kinase-3β (GSK3β). In breast cancer MDA-MB-231 and MDA-MB-468 cells, nanomolar concentrations of prodigiosin decreased phosphorylation of LRP6, DVL2, and GSK3β and suppressed β-catenin-stimulated Wnt target gene expression, including expression of cyclin D1. In MDA-MB-231 breast cancer xenografts and MMTV-Wnt1 transgenic mice, administration of prodigiosin slowed tumor progression and reduced the expression of phosphorylated LRP6, phosphorylated and unphosphorylated DVL2, Ser9 phosphorylated GSK3β, active β-catenin, and cyclin D1. Through its ability to inhibit Wnt/β-catenin signaling and reduce cyclin D1 levels, prodigiosin could have therapeutic activity in advanced breast cancers.prodigiosin | Wnt/beta-catenin signaling | breast cancer | LRP6 | Dishevelled (DVL)

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Section: Discussionmentioning

confidence: 99%

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Wang

Zhou

et al. 2016

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

162

119

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“…It is well documented that DVL1 is an essential mediator of both canonical and non-canonical Wnt pathways 34 . Amplifi cation and increased expression of the DVL1 gene has previously been associated with breast carcinogenesis 19 . However, histological subtypes have not been specifi ed.…”

Section: Discussionmentioning

confidence: 99%

Novel Immunohistochemical Markers for the Differentiation of Lobular and Ductal Invasive Breast Carcinomas

Turashvili¹,

Bouchal²,

Ehrmann³

et al. 2007

BIOMED PAP

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Aims. Invasive ductal and lobular carcinomas are the most common histological types of breast cancer. The loss of E-cadherin expression has been suggested to be the most reliable marker for invasive lobular carcinoma. The aim of our study was to identify the diagnostic usefulness of novel markers in the diff erentiation of these tumor types.Methods. We examined tissue microarrays (TMA) which were constructed from surgical specimens of 119 breast cancer patients. TMA consisted of 80 ductal carcinomas, 29 lobular carcinomas and special type cancers. TMA sections were stained using standard immunohistochemical methods. Monoclonal mouse antibodies against E-cadherin, cytokeratin 5/6 and 17, and polyclonal mouse antibodies against EMP1, DDR1, PRKCI and DVL1 were used.Results. E-cadherin was absent in 93.3 % of lobular tumors compared with only 15 % of ductal tumors (p < 0.0001). EMP1 and DVL1 were overexpressed in lobular tumors (93.1 % and 96.5 %, respectively), whereas PRKCI and DDR1 were positive in ductal cancers (90 % and 96.2 %, respectively). Reduced expression or absence of both cytokeratins 5/6 and 17 was found in both tumor tissues in comparison to normal terminal duct lobular units (p < 0.0001).Conclusions. Apart from the well-established marker, E-cadherin, proteins examined on TMA slides by immunohistochemistry (EMP1, DVL1, DDR1, PRKCI) may represent novel tissue markers helpful in the diff erentiation of ductal and lobular breast cancers. Further studies with larger sets of patients are desirable, to verify the complete immunohistochemical profi les of various histological types of breast cancer and determine the prognostic and predictive signifi cance of novel markers. BACKGROUND

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“…In mouse, three closely related Dishevelled genes, Dvl-1, Dvl-2, and Dvl-3, have been isolated [11][12][13][14]. Some update studies indicate that amplification and increased expression of the Dvl-1 gene may play some role in human breast carcinogenesis through derangement of the Wnt signaling pathway [15].…”

Section: Introductionmentioning

confidence: 99%

Expression of Dishevelled‐1 in wound healing after acute myocardial infarction: possible involvement in myofibroblast proliferation and migration

Chen

Guo

et al. 2004

J Cellular Molecular Medi

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One of our previous studies indicated that the expression of β‐catenin, which is the key factor of wnt‐frizzled pathway, increased significantly in the ischemic area of the rat heart 7 days after myocardial infarction (MI). Together with the results of other recent studies, we made an assumption that wnt‐frizzled pathway may be involved in the controlled cell proliferation and migration during repair processes after MI. To verify this assumption we tried to investigate the expression of another signal transduction molecule called Dishevelled in wnt‐frizzled pathway during the wound healing process after MI. The left descending coronary arteries of rats were ligated to induce MI. Immunohistochemistry SABC method and in situ hybridization were performed to detect the expression of Dishevelled‐1. The results showed, that one day after MI, Dishevelled‐1 mRNA but not protein expression was detected in the cells at the border zone of the infarction area; 4 days after MI the expression of Dishevelled‐1 increased exclusively and cytoplasmic Dishevelled‐1 was observed not only at the border zone but also in the infarct area; 7 days after MI, it seems that the expression reached its peak, the positive staining even spread into the endothelial and smooth muscle cells of the newly formed and pre‐existing blood vessels in the infarction area; after that the Dishevelled‐1 expression decreased abruptly and could hardly be detected 28 days after MI. Thus cytoplasmic Dishevelled‐1 may be involved in the controlled proliferation and migration of myofibroblasts and vascular endothelial cells, hence play a role during the wound healing process after MI.

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Amplification, up‐regulation and over‐expression of DVL‐1, the human counterpart of the Drosophila disheveled gene, in primary breast cancers

Cited by 112 publications

References 23 publications

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Novel Immunohistochemical Markers for the Differentiation of Lobular and Ductal Invasive Breast Carcinomas

Expression of Dishevelled‐1 in wound healing after acute myocardial infarction: possible involvement in myofibroblast proliferation and migration

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