Expression of Wnt4 in Human Pituitary Adenomas Regulates Activation of the β-Catenin-Independent Pathway

Miyakoshi, Tatsuyoshi; Takei, Mao; Kajiya, Hanako; Egashira, Noboru; Takekoshi, Susumu; Teramoto, Akira; Osamura, R. Yoshiyuki

doi:10.1007/s12022-008-9048-9

Cited by 47 publications

(51 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Wnt4 was recently found to be highly expressed in several human pituitary adenoma types, including lactotroph, somatotroph and thyrotroph adenomas (Miyakoshi et al, 2008). The authors of that report speculated that Wnt4 might be involved in proliferation of those cell lineages, and the present findings support the general hypothesis that Wnt4 is involved in plasticity of function and structure in the adult pituitary gland.…”

Section: Discussionsupporting

confidence: 86%

“…Furthermore, a constitutively active mutant -catenin protein, which markedly activated TCFand LEF-dependent transcriptional signaling in HEK-293 cells, had no effect in pituitary GH3 cells. We have found no evidence for nuclear localization of -catenin in GH3 cells, in primary cultures of rat pituitary cells or in intact rat pituitary tissue (data not shown), and similarly no evidence has been found for nuclear expression of -catenin in those pituitary adenomas that displayed Wnt4 overexpression (Miyakoshi et al, 2008).…”

Section: Discussionmentioning

confidence: 63%

“…Semba and colleagues (Semba et al, 2001) found frequent nuclear accumulation of -catenin in 57% of the human pituitary adenomas that they studied. However, in a similar study using 54 human pituitary adenomas, Miyakoshi and colleagues (Miyakoshi et al, 2008) found that, although Wnt4 expression was increased in adenomas producing growth hormone (GH), thyroidstimulating hormone (TSH) and PRL, -catenin was restricted to the cell membrane and was never found in the nucleus, suggesting a non-canonical action of Wnt4 (Miyakoshi et al, 2008). The same group also reported that Wnt4 was specifically expressed in the majority of somatotrophs and in a few thyrotrophs in the untreated rat pituitary, and that estrogen increased Wnt4 expression in these cell types (Miyakoshi et al, 2009).…”

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Wnt signaling in estrogen-induced lactotroph proliferation

Giles

Friedrichsen

et al. 2011

Journal of Cell Science

View full text Add to dashboard Cite

SummaryProlactinomas are the most common type of functioning pituitary adenoma in humans, but the control of lactotroph proliferation remains unclear. Here, using microarray analysis, we show that estrogen treatment increased expression of Wnt4 mRNA in adult Fischer rat pituitary tissue. Dual immunofluorescence analysis revealed that Wnt4 expression was not confined to lactotrophs, but that it was expressed in all anterior pituitary cell types. Estradiol induced proliferation in the somatolactotroph GH3 cell line, in parallel with Wnt4 mRNA and protein induction. A reporter gene assay for TCF-and LEF-dependent transcription revealed that there was no activation of the canonical Wnt pathway in GH3 cells upon stimulation with Wnt-conditioned culture medium or coexpression of constitutively active mutant -catenin. Expression of -catenin in both GH3 cells and normal rat anterior pituitary cells was restricted to the cell membrane and was unaltered by treatment with estradiol, with no nuclear -catenin being detected under any of the conditions tested. We show for the first time that Wnt4 affects non-canonical signaling in the pituitary by inhibiting Ca 2+ oscillations in GH3 cells, although the downstream effects are as yet unknown. In summary, Wnt4 is expressed in the adult pituitary gland, and its expression is increased by estrogen exposure, suggesting that its involvement in adult tissue plasticity is likely to involve -cateninindependent signaling pathways.

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Wnt signaling in estrogen-induced lactotroph proliferation

Giles

Friedrichsen

et al. 2011

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Increased expression of WNT4 has been observed in somatotropinomas, prolactinomas and thyrotropinomas when compared to normal pituitary tissue (Miyakoshi et al 2008, Chambers et al 2013. Since no change in subcellular β-catenin distribution was seen, it was proposed that the non-canonical WNT pathway is activated in these PIT1 lineage tumors, in agreement with WNT4 being a typical ligand in this pathway.…”

Section: Dysregulation Of Wnt In Pituitary Tumorigenesismentioning

confidence: 89%

Pituitary stem cell regulation: who is pulling the strings?

Cox

Roose

Vennekens

et al. 2017

Journal of Endocrinology

View full text Add to dashboard Cite

The pituitary gland plays a pivotal role in the endocrine system, steering fundamental processes of growth, metabolism, reproduction and coping with stress. The adult pituitary contains resident stem cells, which are highly quiescent in homeostatic conditions. However, the cells show marked signs of activation during processes of increased cell remodeling in the gland, including maturation at neonatal age, adaptation to physiological demands, regeneration upon injury and growth of local tumors. Although functions of pituitary stem cells are slowly but gradually uncovered, their regulation largely remains virgin territory. Since postnatal stem cells in general reiterate embryonic developmental pathways, attention is first being given to regulatory networks involved in pituitary embryogenesis. Here, we give an overview of the current knowledge on the NOTCH, WNT, epithelial-mesenchymal transition, SHH and Hippo pathways in the pituitary stem/progenitor cell compartment during various (activation) conditions from embryonic over neonatal to adult age. Most information comes from expression analyses of molecular components belonging to these networks, whereas functional extrapolation is still very limited. From this overview, it emerges that the 'big five' embryonic pathways are indeed reiterated in the stem cells of the 'lazy' homeostatic postnatal pituitary, further magnified en route to activation in more energetic, physiological and pathological remodeling conditions. Increasing the knowledge on the molecular players that pull the regulatory strings of the pituitary stem cells will not only provide further fundamental insight in postnatal pituitary homeostasis and activation, but also clues toward the development of regenerative ideas for improving treatment of pituitary deficiency and tumors.

show abstract

“…Our results show that the wound microenvironment can enhance the expression of Wnt-1, Wnt-4, and Wnt-7a and activate b-catenindependent Wnt pathway signals in grafted ultrathin epidermal sheets. Wnt-1 and Wnt-7a are b-catenin-dependent Wnts, but Wnt-4 is a b-catenin-independent Wnt (Miyakoshi et al, 2008;Kiesslich et al, 2010). The increased Wnt-4 expression might inhibit the over-activation of the b-catenin-dependent Wnt pathway by activating the b-catenin-independent Wnt pathway (Huelsken & Behrens, 2002).…”

Section: Discussionmentioning

confidence: 99%

Wnt/β‐catenin signaling is critical for dedifferentiation of aged epidermal cells in vivo and in vitro

et al. 2011

View full text Add to dashboard Cite

SummaryAged epidermal cells have the capacity to dedifferentiate into stem cell-like cells. However, the signals that regulate the dedifferentiation of aged epidermal cells remain unclear. Here, we provide evidence that Wnt/b-catenin is critical for aged epidermal cell dedifferentiation in vivo and in vitro. Some aged epidermal cells in human ultrathin epidermal sheets lacking basal stem cells transplanted onto wounds dedifferentiated into stem cell-like cells that were positive for CK19 and b1 integrin but negative for CK10. In addition, Wnt/b-catenin pathway was activated during this process. There was increased expression of Wnt-1, Wnt-4, Wnt-7a, b-catenin, cyclin D1, and c-myc. Secreted frizzled-related protein 1, a Wnt/b-catenin pathway inhibitor, blocked dedifferentiation in vivo. Then, the activator, a highly specific glycogen synthase kinase (GSK)-3b inhibitor, of Wnt/b-catenin pathway was added to the culture medium of aged epidermal cells. Surprisingly, we found that the activator induced higher expression of CK19, b1 integrin, Oct4, and Nanog proteins. The induced aged epidermal cells exhibited high colony-forming efficiency, long-term proliferative potential and could regenerate a skin equivalent (as do epidermal stem cells). These results suggested that activation of Wnt/b-catenin pathway induced the dedifferentiation of aged epidermal cells, which suggest a new approach to generate epidermal stem cell-like cells.

show abstract

Expression of Wnt4 in Human Pituitary Adenomas Regulates Activation of the β-Catenin-Independent Pathway

Cited by 47 publications

References 45 publications

Wnt signaling in estrogen-induced lactotroph proliferation

Wnt signaling in estrogen-induced lactotroph proliferation

Pituitary stem cell regulation: who is pulling the strings?

Wnt/β‐catenin signaling is critical for dedifferentiation of aged epidermal cells in vivo and in vitro

Contact Info

Product

Resources

About