Localization and Quantification of Wnt-2 Gene Expression in Mouse Mammary Development

Bühler, Thomas A.; Dale, Trevor; Kieback, C. C.; Humphreys, Robin; Rosen, Jeffrey M.

doi:10.1006/dbio.1993.1009

Cited by 72 publications

(40 citation statements)

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“…The role of Wnt signaling in mammary morphogenesis is suggested by the differential expression of Wnt ligands at distinctive development stages and at different locations within the mammary ductal tree, supporting potential non-redundant Wnt functions in tissue patterning and homeostasis (42)(43)(44)(45). Knock-out of Wnt4, Lrp5, or Lrp6 genes severely block mammary ductal branching and terminal bud formation (12,46,47).…”

Section: Discussionmentioning

confidence: 94%

SOX9 Regulates Low Density Lipoprotein Receptor-related Protein 6 (LRP6) and T-cell Factor 4 (TCF4) Expression and Wnt/β-catenin Activation in Breast Cancer

Wang

et al. 2013

Journal of Biological Chemistry

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Background: Mechanism of enhanced Wnt/␤-catenin activation in breast cancer (BCa) is not fully characterized. Results: SOX9 was highly expressed in basal-like BCa. SOX9 maintained and enhanced LRP6 and TCF4 transcription and Wnt/␤-catenin activation in vitro and in vivo. Conclusion: SOX9 supports a positive feedback loop to sustain Wnt/␤-catenin signal. Significance: The results reveal a new mechanism of Wnt/␤-catenin pathway activation in BCa.

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Section: Discussionmentioning

confidence: 94%

SOX9 Regulates Low Density Lipoprotein Receptor-related Protein 6 (LRP6) and T-cell Factor 4 (TCF4) Expression and Wnt/β-catenin Activation in Breast Cancer

Wang

et al. 2013

Journal of Biological Chemistry

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“…In contrast, they observed that Wnts-5A, -5B and -6 were not detectable in virgin mice, but were dramatically induced during pregnancy. Expression of Wnt-2 has been documented in the myoepithelial compartment in mammary ducts, but is also expressed in fat pads devoid of epithelial cells (BuÈ hler et al, 1993;Weber-Hall et al, 1994). Similar to Wnt-10b, Wnt-2, -4 and -7b are expressed before pregnancy, and thus have the potential to regulate branching morphogenesis of the gland.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the patterning of mammary ducts is controlled by local factors which act at close range (Fauklin and DeOme, 1960). Currently, there is evidence for the regulated expression of Wnts-2, -4, -5a, -5b, -6 and -7b, during various phases of mammary gland development (Gavin and McMahon, 1992;BuÈ hler et al, 1993;Weber-Hall et al, 1994). Evidence that Wnt genes play a role in mammary gland development comes from the regulated expression of these genes in key phases of glandular development (Gavin and McMahon, 1992;Weber-Hall et al, 1994), and from the proliferative eects of Wnt genes when overexpressed in mammary epithelial cells (Roelink et al, 1990;Wong et al, 1994;Bradbury et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Wnt-10b directs hypermorphic development and transformation in mammary glands of male and female mice

1997

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Wnt-10b is expressed during the formation of the mammary rudiment in mouse embryos and its expression continues through puberty when the mammary ductal pattern is established under control of ovarian steroids. Recently, viral activation of the Wnt-10b locus has linked its overexpression to mammary tumor formation, suggesting a role for Wnt-10b in patterning and growth-regulation of the mammary gland. To test this notion, we created lines of transgenic mice that express elevated levels of Wnt-10b under the control of the MMTV promoter/enhancer. Overexpression of this gene resulted in profound developmental alterations in the mammary gland, including expanded glandular development and the precocious appearance of alveoli in virgin females. Moreover, transgenic male mice also exhibited dramatic mammary development involving highly branched mammary ducts and gynecomastia. Aberrant expression of Wnt-10b in the mammary rudiments of males evidently bypasses the normal requirement for ovarian hormonal control in stimulating mammary ductal growth and the repressive eects of androgens. In addition to these developmental eects, transgenic mice of both sexes were highly susceptible to the development of mammary adenocarcinomas. Such tumors arose in a solitary manner indicating that Wnt10b is a proto-oncogene which provides a necessary, but insucient signal for oncogenesis. Relevant to this, there was no evidence of ampli®ed expression of FGF mRNAs in these tumors though the Fgf's are a class of genes often implicated as collaborators in Wnt-mediated tumor formation. Indeed, co-expression of MMTV-Wnt10b and MMTV-FGF-3/int-2 resulted in sterile ospring with highly disorganized mammary epithelium, demonstrating a potent interaction between their respective developmental pathways. These results suggest that Wnt-10b, or other Wnt genes expressed early in mammary development, play a role in regulating sexual dimorphism and show potent transforming activity when overexpressed.

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“…Several members of the Wnt family are differentially expressed during mammary development (Buhler et al, 1993;Gavin and McMahon, 1992;Lane and Leder, 1997;WeberHall et al, 1994). However, with the exception of Wnt4, their functions have not been studied yet.…”

Section: Introductionmentioning

confidence: 99%

Targeted activation of β-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia

et al. 2005

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Wnt/β-catenin signaling pathway is involved in the maintenance of the progenitor cell population in the skin, intestine and other tissues, and its aberrant activation caused by stabilization of β-catenin contributes to tumorigenesis. In the mammary gland, constitutive activation of Wnt/β-catenin signaling in luminal secretory cells results in precocious lobuloalveolar differentiation and induces adenocarcinomas, whereas the impact of this signaling pathway on the function of the second major mammary epithelial cell lineage, the basal myoepithelial cells, has not been analyzed. We have used the keratin (K) 5 promoter to target the expression of stabilized N-terminally truncated β-catenin to the basal cell layer of mouse mammary epithelium. The transgenic mice presented an abnormal mammary phenotype:precocious lateral bud formation, increased proliferation and premature differentiation of luminal epithelium in pregnancy, persistent proliferation in lactation and accelerated involution. Precocious development in pregnancy was accompanied by increased Myc and cyclin D1 transcript levels, and a shift in p63 variant expression towards the ΔNp63 form. The expression of ECM-degrading proteinases and their inhibitors was altered in pregnancy and involution. Nulliparous transgenic females developed mammary hyperplasia that comprised undifferentiated basal (K5/14-positive, K8- and α-smooth muscle-actin-negative) cells. Multiparous mice, in addition, developed invasive basal-type carcinomas. Thus, activation of β-catenin signaling in basal mammary epithelial cells affects the entire process of mammary gland development and induces amplification of basal-type cells that lack lineage markers, presumably, a subpopulation of mammary progenitors able to give rise to tumors.

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Localization and Quantification of Wnt-2 Gene Expression in Mouse Mammary Development

Cited by 72 publications

References 0 publications

SOX9 Regulates Low Density Lipoprotein Receptor-related Protein 6 (LRP6) and T-cell Factor 4 (TCF4) Expression and Wnt/β-catenin Activation in Breast Cancer

SOX9 Regulates Low Density Lipoprotein Receptor-related Protein 6 (LRP6) and T-cell Factor 4 (TCF4) Expression and Wnt/β-catenin Activation in Breast Cancer

Wnt-10b directs hypermorphic development and transformation in mammary glands of male and female mice

Targeted activation of β-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia

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