scholarly journals PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Coralie Drelon ◽  
Annabel Berthon ◽  
Isabelle Sahut-Barnola ◽  
Mickaël Mathieu ◽  
Typhanie Dumontet ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Malignant Tumour ◽  
Wnt Signalling ◽  
Tumour Development

scholarly journals WNK regulates Wnt signalling and β-Catenin levels by interfering with the interaction between β-Catenin and GID

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Atsushi Sato ◽  
Masahiro Shimizu ◽  
Toshiyasu Goto ◽  
Hiroyuki Masuno ◽  
Hiroyuki Kagechika ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Therapeutic Target ◽  
E3 Ubiquitin Ligase ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Tumour Development ◽  
Wnt Signalling Pathway

Abstractβ-Catenin is an important component of the Wnt signalling pathway. As dysregulation or mutation of this pathway causes many diseases, including cancer, the β-Catenin level is carefully regulated by the destruction complex in the Wnt signalling pathway. However, the mechanisms underlying the regulation of β-Catenin ubiquitination and degradation remain unclear. Here, we find that WNK (With No Lysine [K]) kinase is a potential regulator of the Wnt signalling pathway. We show that WNK protects the interaction between β-Catenin and the Glucose-Induced degradation Deficient (GID) complex, which includes an E3 ubiquitin ligase targeting β-Catenin, and that WNK regulates the β-Catenin level. Furthermore, we show that WNK inhibitors induced β-Catenin degradation and that one of these inhibitors suppressed xenograft tumour development in mice. These results suggest that WNK is a previously unrecognized regulator of β-Catenin and a therapeutic target of cancer.

scholarly journals Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex

2003 ◽  
Vol 178 (1) ◽  
pp. 149-158 ◽  
Author(s):  
T Suwa ◽  
M Chen ◽  
CL Hawks ◽  
PJ Hornsby
Keyword(s):  
Adrenal Cortex ◽  
Integration Site ◽  
Northern Blotting ◽  
Wnt Signalling ◽  
Signalling Pathways ◽  
Published Data ◽  
Zona Fasciculata ◽  
Zonal Distribution ◽  
Adult Human ◽  
Human And Mouse

The mechanisms underlying the differentiation of the adrenal cortex into zones are unclear. Microarray studies on RNA from microdissected zona reticularis (ZR) and zona fasciculata/zona glomerulosa (ZF/ZG) derived from adult human adrenal glands showed that a gene of the dickkopf family (DKK), DKK3, is differentially expressed in the zones. The Dickkopf proteins are morphogens involved in Wnt signalling. Northern blotting showed higher DKK3 transcript levels in ZF/ZG than ZR samples. In situ hybridization on adult human adrenal gland sections showed that DKK3 expression was much higher in the ZG than in the ZF or ZR. DKK3 expression was also higher in the medulla. We screened for expression of other members of the DKK family and the related Wingless-type mouse mammary tumor virus integration site gene family (WNT), frizzled (FZD), and dishevelled (DVL) gene families. Among dickkopf family members, only DKK3 was expressed at a detectable level in both human and mouse adrenocortical RNA samples. Consistent with previously published data on the effects of Wnt4 gene disruption in the mouse, we found only WNT4 expression within the WNT family in both human and mouse RNA. Northern blotting showed that WNT4 was expressed at a higher level in ZF/ZG cells than in ZR. The higher level of DKK3 and WNT4 expression in ZF/ZG cells was confirmed by real-time PCR. In the frizzled and dishevelled families we found FZD1, FZD2 and DVL3 transcripts in human adrenocortical RNA, and FZD2 and DVL3 in mouse adrenocortical RNA. These data show that a variety of genes of the Wnt signalling pathways are expressed in the adrenal cortex. The zonal distribution of DKK3 expression suggests that it could be involved in zonal differentiation or growth.

scholarly journals Isolation of Δ3:5-androstadiene-17-one from the urine of a man with a malignant tumour of the adrenal cortex

1937 ◽  
Vol 31 (6) ◽  
pp. 950-961 ◽  
Author(s):  
Harold Burrows ◽  
James Wilfred Cook ◽  
Edna Margaret Frances Roe ◽  
Frederick Lloyd Warren
Keyword(s):  
Adrenal Cortex ◽  
Malignant Tumour

Ultrastructural Cytopiasmic Changes of Adrenal Cortex During Pregnancy

1969 ◽  
Vol 27 ◽  
pp. 298-299
Author(s):  
T. M. Murad ◽  
Karen Israel ◽  
Jack C. Geer
Keyword(s):  
Adrenal Gland ◽  
Steroid Hormones ◽  
Adrenal Cortex ◽  
Lipid Droplets ◽  
Plasma Cholesterol ◽  
Adrenal Steroids ◽  
Dynamic Changes ◽  
Cortical Cells ◽  
Acetyl Coenzyme A ◽  
Adrenal Cortical Cells

Adrenal steroids are normally synthesized from acetyl coenzyme A via cholesterol. Cholesterol is also shown to enter the adrenal gland and to be localized in the lipid droplets of the adrenal cortical cells. Both pregnenolone and progesterone act as intermediates in the conversion of cholesterol into steroid hormones. During pregnancy an increased level of plasma cholesterol is known to be associated with an increase of the adrenal corticoid and progesterone. The present study is designed to demonstrate whether the adrenal cortical cells show any dynamic changes during pregnancy.

Adrenocortical Ultrastructure in Ectopic Acth Syndrome

1976 ◽  
Vol 34 ◽  
pp. 238-239
Author(s):  
K. Kovacs ◽  
E. Horvath ◽  
W. Singer
Keyword(s):  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Ectopic Acth Syndrome ◽  
Pituitary Neoplasms ◽  
Electron Microscopic ◽  
Adrenocortical Cells ◽  
Cell Hyperplasia ◽  
Ectopic Acth ◽  
Ectopic Acth Production ◽  
Microscopic Findings

Secretion of ACTH by non-pituitary neoplasms is recognized with increasing frequency. While the clinical and biochemical changes associated with ectopic ACTH production have been extensively studied recently, relatively little attention was focused on the morphology of the adrenal cortex and, to our knowledge, the fine structure of the adrenocortical cells in cases of ectopic ACTH syndrome has not been described so far. We report here the electron microscopic findings in the adrenal cortex of a 50-year-old man with a pancreatic apudoma. The patient showed the characteristic clinical and biochemical features of ectopic ACTH syndrome and because of extensive hypercorticism, underwent bilateral adrenalectomy.By light microscopy, the adrenal cortices showed extensive compact cell hyperplasia and lipid depletion. The zona glomerulosa was present in small foci and, except for a few places, fasciculata cells were noted under the fibrous capsule.

Surface Ultrastructure of Human Ectocervix in Certain Pathological Conditions

1985 ◽  
Vol 43 ◽  
pp. 570-571
Author(s):  
S. Mukherjee ◽  
T. Guha ◽  
B. Chakrabarti ◽  
P. Chakrabarti
Keyword(s):  
Epithelial Cells ◽  
Marked Reduction ◽  
Squamous Epithelium ◽  
Malignant Tumour ◽  
Surface Ultrastructure ◽  
Normal Tissues ◽  
Pathological Conditions ◽  
Hexagonal Shape ◽  
Columnar Cells ◽  
Scanning Electron

The cervix is an important organ in reproduction. Its malfunction is frequently a factor for infertility. Ectocervix region does not appear to have received much attention although many studies have been reported on the endocervix. We report here our SEM observations on ectocervix in certain pathological conditions compared to normal ectocervix.Ectocervix specimens from human females with specific pathological disorders were processed for Scanning Electron Microscopy by conventional method and they were examined in a Philips SEM.The normal ectocervix is lined by flat layer of squamous epithelial cells with microridges (Fig. 1). These cells are known to be formed from columnar cells through metaplastic transformation. The cells of carcinoma-bearing ectocervix show a disorganised appearance (Fig. 2). In non-malignant tumour surface some cuboidal and few columnar cells were seen (Fig. 3). A cyst appears like an overgrowth on the surface of the squamous epithelium (Fig. 4). In ulcerated ectocervix a marked reduction of epithelial cells are observed (Fig. 5); the cells are devoid of microridges and, the large polygonal cells, as observed in normal tissues, have somehow acquired comparatively small hexagonal shape

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