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At least 19 recordsLinked to original sources
PubMed1995

Biochemical analysis of murine Wnt proteins reveals both shared and distinct properties.

The murine Wnt family of proteins consists of at least 12 members that possess significant amino acid homology. Current evidence suggests that these proteins are secreted cell-signaling molecules which are likely to have multiple roles during both embryonic development and oncogenesis. Although the biochemical properties of Wnt-1 have been thoroughly examined, less is known about the characteristics of other Wnt family members. We have compared the properties of six murine Wnt proteins (Wnt-1, Wnt-3a, Wnt-5a, Wnt-5b, Wnt-6, and Wnt-7b) transiently expressed in COS cells. All members enter the endoplasmic reticulum (ER) and are glycosylated. However, all six Wnt proteins are primarily retained in the ER in association with BiP, a resident ER protein that binds to improperly folded proteins and prevents their secretion and/or promotes proper folding. Although all Wnt family members examined are similarly processed, one notable difference was identified. Whereas addition of suramin to COS cell cultures significantly increases the levels of all six Wnts in the medium, the addition of heparin only influences the levels of Wnt-1, Wnt-6, and Wnt-7b.

Amino Acid Sequence↗
PubMed1993

Isolation of cDNAs for two closely related members of the axolotl Wnt family, Awnt-5A and Awnt-5B, and analysis of their expression during development.

To characterize molecular interactions between cells in the early amphibian embryo, we have isolated cDNAs for two members of the axolotl (Ambystoma mexicanum) Wnt family, Awnt-5A and Awnt-5B. The encoded proteins share 83% amino acid identity. Using a reverse transcription-polymerase chain reaction (RT-PCR) assay, we find that Awnt-5A transcripts are abundant in the blastula until gastrulation, barely detectable during gastrulation, and increase again during neurulation. They are detected throughout the remaining development and in hatched larvae. In contrast, transcripts for Awnt-5B are undetectable in the blastula. They appear with gastrulation, are present throughout neurulation and organogenesis, and decrease to barely detectable levels in hatched larvae. PCR reactions performed using cDNA library-phage DNA templates derived from whole neurulae versus embryos with the neuroectoderm removed suggest that, in the neurula, Awnt-5A transcripts are present in neuroectodermal as well as non-neuroectodermal tissues while Awnt-5B mRNAs are predominantly localized in the neuroectoderm. To localize Awnt-5A expression in embryos before gastrulation, early gastrulae were dissected by cutting along the animal-vegetal and future dorso-ventral axes and analyzed by RT-PCR. At this early stage, Awnt-5A transcripts appear to be predominantly localized in the dorso-vegetal region of the embryo. These results suggest that the two closely related Awnt-5 genes participate in different morphogenetic processes during early axolotl development.

Ambystoma mexicanum↗
PubMed1995

Wnt expression patterns in chick embryo nervous system.

Several lines of evidence suggest that Wnt genes play a critical role in regulating development of the vertebrate embryo. To address the role that this family may play in the development of the chicken central nervous system (CNS), we have used a PCR based strategy to clone partial sequences for Wnt genes. At least six different Wnt genes are expressed in the developing CNS of the chick embryo. The domains of expression overlap either partially or completely, and are expressed in spatial domains that prefigure morphological subunits of the embryonic neural tube. Wnt-1 and Wnt-4 are first expressed in the open neural plate in the region of the presumptive mesencephalon. Wnt-3a expression is first observed in the rhombencephalic regions of the open neural plate. After neural tube closure, when the embryonic subdivisions of the neural tube became apparent, Wnt-1, Wnt-3a and Wnt-4 are all broadly expressed in partially overlapping domains in the mesencephalon and caudal diencephalon, as well as in the rhombencephalon and spinal cord. The mesencephalic expression patterns are subsequently modified such that Wnt-1 and Wnt-4 are expressed in a characteristic ring just rostral to the isthmus, at the mesencephalic/metencephalic junction; and Wnt-1 and Wnt-3a expression become restricted to the dorsal midline. Wnt-1, Wnt-3a, Wnt-4, Wnt-5a and Wnt-8b are expressed in one or two caudal subdivisions of the developing diencephalon, the synencephalon and posterior parencephalon, but do not extend ventral to the zona limitans interparencephalica. In contrast, Wnt-7b is expressed in the anterior parencephalon. Both Wnt-7b and Wnt-8b are expressed in telencephalic portions of the secondary prosencephalon. The timing and spatial distribution of Wnt-gene expression in the chick embryo further support the general hypothesis that Wnt genes play key roles in patterning the developing vertebrate nervous system.

Amino Acid Sequence↗
PubMed1995

Regulation of Wnt5a mRNA expression in human mammary epithelial cells by cell shape, confluence, and hepatocyte growth factor.

The Wnts are a family of genes with a role in cell fate and morphological development in numerous embryonic and adult tissues. In mouse mammary tissue a subset of the Wnts have a function in the normal development of the gland, and aberrant expression of Wnts normally silent in this tissue causes mammary carcinomas. We have previously shown that Wnt5a expression is elevated in the epithelial component of proliferative lesions of human breast and have therefore examined the regulation of Wnt5a mRNA expression in the human mammary epithelial cell line HB2, which has a luminal phenotype and thus represents the most commonly transformed cell type in human breast cancer. Wnt5a was up-regulated 30-fold at confluence. This up-regulation was induced specifically by confluence and not by the growth arrest that accompanied it. In addition, Wnt5a was down-regulated 3-fold by changes in cell shape associated with the transition from growth on a two-dimensional surface (flat cell morphology) to growth in three-dimensional gels (spherical cell morphology). Cytoskeletal disruption with non-toxic doses of colchicine also induced a spherical morphology and brought about a dose-dependent down-regulation of Wnt5a. Wnt5a was also down-regulated 10-fold during the hepatocyte growth factor-induced branching of HB2 cell aggregates in collagen gels. The down-regulation of Wnt5a preceded the branching process. A similar result was obtained with primary human breast epithelial populations and the breast cancer cell line MDA468. We conclude that regulation of Wnt5a expression is a down-stream effect of signaling by hepatocyte growth factor. These results are consistent with a role for Wnt5a in mammary epithelial cell motility and are in accord with Xwnt5a's function in embryonal cell migration. If Wnt5a's function in human mammary epithelial cells is similar to that of Xwnt5a, its up-regulation at confluence may be a mechanism for inhibition of cell migration beyond confluence.

Breast↗
PubMed1996

Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development.

When overexpressed in Xenopus embryos, Xwnt-1, -3A, -8 and -8b define a functional class of Wnts (the Wnt-1 class) that promotes duplication of the embryonic axis, whereas Xwnt-5A, -4, and -11 define a distinct class (the Wnt-5A class) that alters morphogenetic movements (Du, S., S. Purcell, J. Christian, L. McGrew, and R. Moon. 1995. Mol. Cell. Biol. 15:2625-2634). Since come embryonic cells may be exposed to signals from both functional classes of Wnt during vertebrate development, this raises the question of how the signaling pathways of these classes of Wnts might interact. To address this issue, we coexpressed various Xwnts and components of the Wnt-1 class signaling pathway in developing Xenopus embryos. Members of the Xwnt-5A class antagonized the ability of ectopic Wnt-1 class to induce goosecoid expression and a secondary axis. Interestingly, the Wnt-5A class did not block goosecoid expression or axis induction in response to overexpression of cytoplasmic components of the Wnt-1 signaling pathway, beta-catenin or a kinase-dead gsk-3, or to the unrelated secreted factor, BVg1. The ability of the Wnt-5A class to block responses to the Wnt-1 class may involve decreases in cell adhesion, since ectopic expression of Xwnt-5A leads to decreased Ca2+-dependent cell adhesion and the activity of Xwnt-5A to block Wnt-1 class signals is mimicked by a dominant negative N-cadherin. These data underscore the importance of cell adhesion in modulating the responses of embryonic cells to signaling molecules and suggest that the Wnt-5A functional class of signaling factors can interact with the Wnt-1 class in an antagonistic manner.

Animals↗
PubMed1993

Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis.

To contribute to an understanding of the roles and mechanisms of action of Wnts in early vertebrate development, we have characterized the normal expression of Xenopus laevis Wnt-5A, and investigated the consequences of misexpression of this putative signalling factor. Xwnt-5A transcripts are expressed throughout development, and are enriched in both the anterior and posterior regions of embryos at late stages of development, where they are found primarily in ectoderm, with lower levels of expression in mesoderm. Overexpression of Xwnt-5A in Xenopus embryos leads to complex malformations distinct from those achieved by ectopic expression of Xwnts -1, -3A, or -8. This phenotype is unlikely to result from Xwnt-5A acting as an inducing agent, as overexpression of Xwnt-5A does not rescue dorsal structures in UV-irradiated embryos, does not induce mesoderm in blastula caps, and Xwnt-5A does not alter the endogenous patterns of expression of goosecoid, Xbra, or Xwnt-8. To pursue whether Xwnt-5A has the capacity to affect morphogenetic movements, we investigated whether overexpression of Xwnt-5A alters the normal elongation of blastula cap explants induced by activin. Intriguingly, Xwnt-5A blocks the elongation of blastula caps in response to activin, without blocking the differentiation of either dorsal or ventral mesoderm within these explants. The data are consistent with Xwnt-5A having the potential activity of modifying the morphogenetic movements of tissues.

Amino Acid Sequence↗
PubMed1993

Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21.

The highly conserved Wnt genes belong to a widely distributed family of presumptive signaling molecules that have been implicated not only in the regulation of normal pattern formation during embryogenesis and differentiation of cell lineages, but also in oncogenic events. All of the known vertebrate Wnt genes encode for 38- to 43-kDa cysteine-rich putative glycoproteins, which have features typical of secreted growth factors: a hydrophobic signal sequence, a conserved asparagine-linked oligosaccharide consensus sequence, and 22 conserved cysteine residues whose relative spacing is maintained. In this study, we report the cloning and sequencing of several overlapping cDNAs encoding approximately 4.1 kb of the human homologue of Wnt-5A. The mature protein contained 343 residues (M(r) approximately 38,000 excluding any post-translational modifications) with a > 93% homology to the reported sequences of other Wnt-5A proteins (> 99% homologous to mouse Wnt-5A). This protein maintained certain features--a hydrophobic signal sequence, the Wnt-1 family "signature sequence" (CKCHGvSGSC), and a number of other conserved amino acid residues: 24 cysteine residues, 4 asparagine-linked oligosaccharide consensus sequences, and a tyrosine sulfation site--that have been found in all other Wnt-5A proteins. Reverse transcriptase PCR analysis of RNA from a variety of human embryonic, neonatal, and adult cells and/or tissues showed that human Wnt-5A expression was detected only in neonatal heart and lung. It may be relevant, however, that the 3'-untranslated region contained numerous AT-rich motifs that could be involved in the rapid degradation of mRNA. Finally, using a combination of Southern blotting, PCR amplification, and in situ hybridization, the human Wnt-5A (WNT5A) gene was mapped to chromosome 3p14-p21.

Amino Acid Sequence↗
PubMed1996

The limb field mesoderm determines initial limb bud anteroposterior asymmetry and budding independent of sonic hedgehog or apical ectodermal gene expressions.

We have analyzed the pattern of expression of several genes implicated in limb initiation and outgrowth using limbless chicken embryos. We demonstrate that the expressions of the apical ridge associated genes, Fgf-8, Fgf-4, Bmp-2 and Bmp-4, are undetectable in limbless limb bud ectoderm; however, FGF2 protein is present in the limb bud ectoderm. Shh expression is undetectable in limbless limb bud mesoderm. Nevertheless, limbless limb bud mesoderm shows polarization manifested by the asymmetric expression of Hoxd-11, -12 and -13, Wnt-5a and Bmp-4 genes. The posterior limbless limb bud mesoderm, although not actually expressing Shh, is competent to express it if supplied with exogenous FGF or transplanted to a normal apical ridge environment, providing further evidence of mesodermal asymmetry. Exogenous FGF applied to limbless limb buds permits further growth and determination of recognizable skeletal elements, without the development of an apical ridge. However, the cells competent to express Shh do so at reduced levels; nevertheless, Bmp-2 is then rapidly expressed in the posterior limbless mesoderm. limbless limb buds appear as bi-dorsal structures, as the entire limb bud ectoderm expresses Wnt-7a, a marker for dorsal limb bud ectoderm; the ectoderm fails to express En-1, a marker of ventral ectoderm. As expected, C-Lmx1, which is downstream of Wnt-7a, is expressed in the entire limbless limb bud mesoderm. We conclude that anteroposterior polarity is established in the initial limb bud prior to Shh expression, apical ridge gene expression or dorsal-ventral asymmetry. We propose that the initial pattern of gene expressions in the emergent limb bud is established by axial influences on the limb field. These permit the bud to emerge with asymmetric gene expression before Shh and the apical ridge appear. We report that expression of Fgf-8 by the limb ectoderm is not required for the initiation of the limb bud. The gene expressions in the pre-ridge limb bud mesoderm, as in the limb bud itself, are unstable without stimulation from the apical ridge and the polarizing region (Shh) after budding is initiated. We propose that the defect in limbless limb buds is the lack of a dorsal-ventral interface in the limb bud ectoderm where the apical ridge induction signal would be received and an apical ridge formed. These observations provide evidence for the hypothesis that the dorsal-ventral ectoderm interface is a precondition for apical ridge formation.

Animals↗
PubMed1995

Aberrant expression of the growth factor Wnt-5A in human malignancy.

The Wnt-5A gene codes for a secreted cysteine-rich growth factor that mediates cell to cell signaling via a paracrine mechanism during development and ontogeny. We have recently determine the genomic organization and chromosomal mapping of the human Wnt-5A, and observed distinct patterns of expression in developing human embryos. In this report, we have performed a detailed expression analysis of 100 adult human tissues and tumors and 10 human cell lines. Our data show a widespread expression of Wnt-5A in adult tissues and cells, and aberrant mRNA levels in lungs, breast, and prostate carcinomas and in melanomas. The up-regulation of Wnt-5A in human malignancy was not due to either gene rearrangement or amplification. These findings document an abnormal expression of this growth factor in malignancy and implicate Wnt-5A in the genesis of human cancer.

Gene Expression Regulation, Neoplastic↗
PubMed1994

Regulated expression of Wnt family members during proliferation of C57mg mammary cells.

At least six members of the Wnt gene family are expressed in the murine mammary gland during growth and differentiation, whereas several other Wnt family members participate in malignant transformation of this tissue. We have used the C57mg mammary cell line, which naturally expresses the Wnt-4 and Wnt-5a genes, to examine Wnt gene expression during proliferation. The data show that the growth factors basic fibroblast growth factor, transforming growth factor beta 1, and epidermal growth factor are mitogenic for C57mg cells, and partial transformation by Wnt-1 can substitute for the proliferative signal provided by these factors. Several different mitogenic stimuli selectively down-modulate the levels of endogenous Wnt-4 and Wnt-5a RNA in C57mg cells. Partial transformation by either Wnt-1 or Wnt-2 is accompanied by a dramatic decrease in Wnt-4 RNA and a small decrease in Wnt-5a RNA. Mitogenic stimulation by basic fibroblast growth factor or partial transformation by Int-2, a fibroblast growth factor family member, also leads to a selective decrease in the levels of endogenous Wnt RNA. No expression of the Wnt-4 and Wnt-5a genes is detectable in C57mg cells that are fully transformed by the activated tyrosine kinase oncogene Neu. In contrast, overexpression of Wnt-5a in C57mg cells does not lead to a transformed phenotype and is not accompanied by a decrease in endogenous Wnt-4 RNA levels. Overexpression of Wnt-5a does lead to a small decrease in endogenous Wnt-5a levels, perhaps through autoregulation. These data indicate that Wnt-4 and Wnt-5a expression in mammary cells is responsive to growth regulatory signals, and the down-modulation of expression of either or both genes correlates with cell proliferation. The inverse correlation between expression of the endogenous Wnt genes and cell proliferation suggests that Wnt-4 and Wnt-5a may participate in restricting the proliferation of C57mg cells.

Animals↗
PubMed1995

Characterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis.

We report the complete genomic organization of the human WNT-5A gene, which encodes a cysteine-rich growth factor involved in cell-cell signaling during growth and differentiation. The gene comprises five exons with the terminal exon coding for a large 3'-untranslated region of approximately 6.5 kilobase pairs and utilizes multiple polyadenylation signals to generate at least four discrete transcripts. We discovered a new leader exon interrupted by a 411-base pair intron that was retained in our original cDNA cloning. The promoter region was located in a GpC-rich island and harbored numerous cis-acting elements including several GC boxes and Sp1, AP1, and AP2 binding motifs. It lacked TATA or CAAT boxes typical of housekeeping and growth factor genes. In support of this, primer extension revealed extension two transcription start sites. Transient cell transfection assays showed functional promoter activity for the 3.9-kilobase pair 5'-flanking region. Interestingly, internal and 5' deletions revealed tha the distal promoter was not required for full transcriptional activity and that the first 631 base pairs of WNT-5A harbored the strongest promoter activity. Using a panel of rodent-human hybrid DNAs carrying portions of chromosome 3p, we mapped the gene to 3p14.2-p21.1, between a constitutional and a familial renal cell carcinoma-associated translocation. In situ hybridization analyses of early human embryos at 28-42 days of gestation revealed that WNT-5A transcripts were not restricted to the developing brain and limbs but were also observed in the mesenchyme bordering the pharyngeal clefts and pouches and in the developing gonads and kidneys. The relatively high expression in the celomic epithelium and in the precursors of follicles and seminiferous tubules suggest a novel role for WNT-5A in germ-cell differentiation. This study provides the molecular basis for discerning the regulation of the WNT-5A gene and offers the opportunity to investigate genetic disorders linked to this important gene.

Animals↗
PubMed2026

Single-cell profiling decodes patagium development in gliding mammal.

The gliding patagium represents a key adaptation for mammalian flight, but its cellular development remains unexplored. Using single-nucleus RNA sequencing of embryonic flying squirrel patagium and dorsal skin, we construct a single-cell atlas of patagium development and identify two distinct fibroblast subpopulations (Fp2 and Fr) highly enriched in the patagium. These fibroblasts are characterized by the patagium upregulation of Wnt5a, Fgf7, and Fgf10, and are associated with patagium morphogenesis through dermal-epidermal putative communication interactions between dermal fibroblasts (Fp2 and Fr) and epithelial basal keratinocytes. Specifically, Fp2 fibroblasts are potentially involved in distal dermal condensation and epithelial thickening together with elevated Wnt5a expression, while both Fp2 and Fr fibroblasts could play a role in epithelial polarization and thickening through Fgf7 and Fgf10, as suggested by ex vivo assays. Our data suggest that gliding patagium development results from the co-option of conserved WNT and FGF signaling pathways within a specialized fibroblast-epithelial context, illustrating how modifications of conserved developmental programs give rise to derived morphological traits.

Animals↗
PubMed1994

Alterations in gene expression during mesoderm formation and axial patterning in Brachyury (T) embryos.

The mouse T (Brachyury) deletion causes defective mesoderm formation and notochord morphogenesis, and abnormalities in the caudal neural tube and somites. To investigate the effect of the wild type T gene on concurrently expressed genes, we have compared expression of a panel of such genes in homozygous T mutants with that in wild type and heterozygous T/+ control embryos. Two classes of genes were used in this study: those implicated in primitive streak or mesoderm formation, and those which are differentially expressed in regions of the neural tube and somites. Results of wholemount in situ analysis show that the mRNA levels of Evx-1, Wnt-3a and Wnt-5a decrease in T/T embryos late in gastrulation, although earlier expression patterns are similar to control embryos. In contrast, BMP-4 and Msx-1 expression patterns remain similar throughout the period studied. Pax-3 and Pax-6, which are expressed in specific dorsoventral domains of the neural tube, both have ventrally extended expression domains in caudal T/T neural tube. This is consistent with a missing ventral signal provided by the notochord. However, the expression of Msx-1 in the most dorsal domain of the neural tube is unaltered in T/T embryos. Pax-1 and Pax-3, which are expressed in the sclerotome and dermamyotome respectively, are expressed correctly in anterior T/T somites, although the Pax-3 expression domain is widened ventromedially. This extension into ventromedial somite domains is more pronounced caudally, supporting a function for the notochord in ventralizing somites.

Abnormalities, Multiple↗
PubMed1993

Localization and quantification of Wnt-2 gene expression in mouse mammary development.

The Wnt gene family encodes a group of proteins probably involved in cell-cell communication during several stages of vertebrate development. More than 10 members of this family have been identified and shown to be expressed mainly in developing neural tissue. Using a reverse transcription-polymerase chain reaction (RT-PCR)-based approach with degenerate oligonucleotides directed against conserved sequences in the Wnt genes, Wnt-2 transcripts were detected in RNA isolated from mammary glands of 4- to 6-week-old virgin C3H mice, a period characterized by extensive end bud and ductal proliferation. The spatial and temporal expression of Wnt-2 in the developing mouse mammary gland was studied by in situ hybridization, quantitative RT-PCR, and Northern analysis. Wnt-2 is expressed during the ductal phase of mammary gland development, primarily in the basal layer of mammary ducts and in the body cells of end buds. Wnt-2 RNA transcripts were readily detected in poly(A) RNA isolated from 5-week-old C3H and Balb/c mice. RNA transcript levels measured as molecules per nanogram of total RNA by RT-PCR decreased 10- to 40-fold within 2 days after the onset of pregnancy and remained low during pregnancy and lactation. This is in contrast to the patterns of expression of other Wnt family members, Wnt-5a and -5b, whose expression was either barely or not detectable in the 4- to 6-week-old mammary gland, but increased markedly during pregnancy. These results confirm the differential expression of Wnt gene family members during mammary gland development. Furthermore, they suggest that Wnt-2, as well as several other family members, may play a role in pattern formation during early mammary gland development.

Animals↗
PubMed1992

Cloning and characterization of a novel Drosophila Wnt gene, Dwnt-5, a putative downstream target of the homeobox gene distal-less.

The Wnt gene family in vertebrates comprises at least 11 distinct genes but the only family member previously identified in Drosophila has been the segment polarity gene wingless (wg), the ortholog of vertebrate Wnt-1. In this report we describe the isolation of a novel Drosophila Wnt gene, Dwnt-5, which differs significantly from wg in both the pattern of its expression during embryogenesis and the predicted structure of its product. Dwnt-5 encodes a polypeptide of 112 kDa, which is more than twice as large as the products of previously known Wnt genes. The protein shares homology with other Wnt sequences in its carboxy-terminal half only and is most closely related to the products of vertebrate Wnt-5a and Wnt-5b. Dwnt-5 is expressed in a complex pattern during Drosophila embryogenesis. At the extended germ band stage, however, transcripts accumulate specifically in the nascent limb primordia of the head and thoracic segments. We show that this elevated expression depends on the activity of the homeobox gene Distal-less (Dll) and suggest that the Dwnt-5 gene may constitute a downstream target of Dll that acts in the specification of these primordia.

Amino Acid Sequence↗
PubMed1994

Developmental and hormonal regulation of Wnt gene expression in the mouse mammary gland.

Ectopic expression of Wnt-1 in the mammary epithelium causes hyperplasias and increases the frequency of tumour formation. Other members of the Wnt gene family are naturally expressed in the breast and are thought to be involved in controlling mammary gland development. Using Northern and in-situ hybridisation, differential expression of Wnt-2, Wnt-4, Wnt-5a, Wnt-5b, Wnt-6 and Wnt-7b in epithelial and mesenchymal compartments was observed. Complex patterns of Wnt expression were found during the ductal, lobulo-alveolar and involution phases of development. Finally, Wnt-2, Wnt-4 and Wnt-5b were shown to be regulated by ovarian hormones. These results suggest that Wnt genes have non-redundant roles in breast development and may be involved in the hormonal regulation of mammary growth.

Age Factors↗
PubMed1994

Differential transformation of mammary epithelial cells by Wnt genes.

The mouse Wnt family includes at least 10 genes that encode structurally related secreted glycoproteins. Wnt-1 and Wnt-3 were originally identified as oncogenes activated by the insertion of mouse mammary tumor virus in virus-induced mammary adenocarcinomas, although they are not expressed in the normal mammary gland. However, five other Wnt genes are differentially expressed during development of adult mammary tissue, suggesting that they may play distinct roles in various phases of mammary gland growth and development. Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis. We have tested Wnt family members for the ability to induce transformation of cultured mammary cells. The results demonstrate that the Wnt gene family can be divided into three groups depending on their ability to induce morphological transformation and altered growth characteristics of the C57MG mammary epithelial cell line. Wnt-1, Wnt-3A, and Wnt-7A were highly transforming and induced colonies which formed and shed balls of cells. Wnt-2, Wnt-5B, and Wnt-7B also induced transformation but with a lower frequency and an apparent decrease in saturation density. In contrast, Wnt-6 and two other family members which are normally expressed in C57MG cells, Wnt-4 and Wnt-5A, failed to induce transformation. These data demonstrate that the Wnt genes have distinct effects on cell growth and should not be regarded as functionally equivalent.

Animals↗