Identification of the mammary line in mouse by <i>Wnt10b</i> expression

Veltmaat, Jacqueline M.; Veelen, Wendy van; Thiery, Jean Paul; Bellusci, Saverio

doi:10.1002/dvdy.10441

Cited by 121 publications

(137 citation statements)

References 15 publications

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“…As expected, the kinase inhibitors did not alter the levels of GSK3[3, but they did upregulate 13-catenin expression as well as cyclin Dl, consistent with inhibition of GSK activity and activation of Wnt signaling (Fig. 5B, C Glycogen synthase kinase 3P (GSK3I3) is a serine/threonine and buds beginning on embryonic day 11.25 and are essential for kinase that was originally found to have a pivotal role in glycogen initiation of mammary morphogenesis (15,16). LEF-1 is expressed metabolism and insulin-mediated signaling but is now recognized in the mammary gland beginning at embryonic day 11.5, and in to function in multiple biological pathways.…”

Section: Introductionsupporting

confidence: 69%

The Role of DN-GSK3Beta in Mammary Tumorigenesis

Farago¹

2005

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE 3. DATES COVERED (From -To) PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Boston Medical CenterBoston, MA 02118 SPONSORING I MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S)12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTRecent studies have implicated ectopic activation of the Wnt pathway in many human cancers, including breast cancer. 13-catenin is a critical co-activator in this signaling pathway, and is regulated in a complex fashion by phosphorylation, degradation, and nuclear translocation. Glycogen synthase kinase-3[3 (GSK3[P) phosphorylation of the N-terminal domain of 03-catenin targets it for ubiquitination and proteosomal degradation. We hypothesized that expression of dominant negative (DN) GSK30 in mammary glands would function in a dominant negative fashion by antagonizing the endogenous activity of GSK3[3 and promoting breast cancer development. Consistent with this, we find that DN-GSK3P stabilizes [-catenin expression, catalyzes its localization to the nucleus, and upregulates the downstream target gene, cyclin D 1, in vitro. In vivo, transgenic mice overexpressing the DN-GSK3 3 under the control of the MMTV-LTR develop mammary tumors with over-expression of 13-catenin and cyclin D 1. Thus, antagonism of GSK3 P activity is oncogenic in the mammary epithelium; mutation or pharmacologic downregulation of GSK3P3 could promote mammary tumors. 3-catenin is the critical co-activator in this signaling pathway, and is regulated in a complex fashion by phosphorylation, nuclear translocation, and degradation. Glycogen synthase kinase-3[3 (GSK33) phosphorylation of the N-terminal domain of 3-catenin targets P3-catenin for ubiquitination and proteosomal degradation. While a role for the Wnt pathway is well-recognized in colon cancer, where for example mutations of the APC and 13-catenin genes are found in both s...

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Section: Introductionsupporting

confidence: 69%

The Role of DN-GSK3Beta in Mammary Tumorigenesis

Farago¹

2005

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“…S1a). We found that among 10 Wnt candidates that had been reportedly expressed in the mammary gland (Weber-Hall et al 1994;Chu et al 2004;Veltmaat et al 2004;Dwyer et al 2010), Wnt4, Wnt5A, Wnt5B, and Wnt7B were detected in luminal cells by qPCR. Among them, Wnt4 and Wnt7B showed predominant expression in luminal cells (Supplemental Fig.…”

Section: Luminal Cells Produce Rspo1mentioning

confidence: 89%

R-spondin1 is a novel hormone mediator for mammary stem cell self-renewal

et al. 2014

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Signals from the niche play pivotal roles in regulating adult stem cell self-renewal. Previous studies indicated that the steroid hormones can expand mammary stem cells (MaSCs) in vivo. However, the facilitating local niche factors that directly contribute to the MaSC expansion remain unclear. Here we identify R-spondin1 (Rspo1) as a novel hormonal mediator in the mammary gland. Pregnancy and hormonal treatment up-regulate Rspo1 expression. Rspo1 cooperates with another hormonal mediator, Wnt4, to promote MaSC self-renewal through Wnt/b-catenin signaling. Knockdown of Rspo1 and Wnt4 simultaneously abolishes the stem cell reconstitution ability. In culture, hormonal treatment that stimulates the expression of both Rspo1 and Wnt4 can completely substitute for exogenous Wnt proteins, potently expand MaSCs, and maintain their full development potential in transplantation. Our data unveil the intriguing concept that hormones induce a collaborative local niche environment for stem cells.

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“…Individual gene expression analysis revealed that the relative expression of known early mammary epithelial markers such as Wnt10b (Veltmaat et al, 2004), Gata3 (Asselin-Labat et al, 2007), Nrg3 (Howard et al, 2005), Pthlh (Dunbar et al, 1999), Edar (Pispa et al, 2003), Msx1 (Phippard et al, 1996), and b-catenin (Chu et al, 2004), was indeed high in the mammary bud samples. Furthermore, expression of genes known to be expressed in the dermal and mammary mesenchyme such as Fgf7, Pthlh receptor (Pth1r), Twist2, or in the mammary mesenchyme only, such as Estrogen receptor (Esr1) and Androgen receptor (Ar) (Dillon et al, 2004, Dunbar et al, 1999, Heckman et al, 2007, Li et al, 1995, was high in the mesenchymal samples (Fig.…”

Section: Immuno-detection Of Protein Expressionmentioning

confidence: 99%

A non-enzymatic microsurgical dissection technique of mouse embryonic tissues for gene expression profiling applications

Sun¹,

Lee²,

Veltmaat³

2011

Int. J. Dev. Biol.

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With the increased use of gene expression profiling to identify molecular regulators of cellular and developmental mechanisms, developmental biologists face a new challenge in dissecting tissues without cross-contamination or change in RNA profile, and with intact RNA integrity. We have developed a technique that overcomes these problems. We took the dissection of rudimentary mouse embryonic mammary glands as an example, as these structures are particularly difficult to separate from their contiguous ectoderm and strongly adhering mesenchyme. Contrary to conventional enzymatic tissue-separation methods, we blocked transcriptional activity prior to dissection and protected RNA from degradation during dissection, by the use of RNAlater. While RNAlater dehydrates specimens so severely that it interferes with visibility and clean dissection of organs or tissues, we established rehydration conditions that in fact facilitated tissue separation and shortened dissection time to about 10 minutes. The extracted RNA had an excellent quality, rendering it perfectly suitable for transcriptional profiling. Visual inspection of separated tissues and tissue specific gene expression analysis by microarray and RT-PCR confirmed that the tissues were separated with minimal or no cross-contamination. We show that this dissection method can be applied to a broad variety of organs, and that the tissue is still amenable to protein detection. In conclusion, this is a rapid, cheap and effective non-enzymatic tissue separation method which greatly facilitates the exploration of molecular mechanisms in organ formation.

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Identification of the mammary line in mouse by Wnt10b expression

Cited by 121 publications

References 15 publications

The Role of DN-GSK3Beta in Mammary Tumorigenesis

The Role of DN-GSK3Beta in Mammary Tumorigenesis

R-spondin1 is a novel hormone mediator for mammary stem cell self-renewal

A non-enzymatic microsurgical dissection technique of mouse embryonic tissues for gene expression profiling applications

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