Changes in receptor location affect the ability of oxytocin to stimulate proliferative growth in prostate epithelial cells

2019 ◽  
Vol 31 (6) ◽  
pp. 1166 ◽  
Author(s):  
M. L. Gould ◽  
H. D. Nicholson
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Cell Membrane ◽  
Lipid Rafts ◽  
Protein Interactions ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Protein Protein Interactions ◽  
Normal Prostate ◽  
Prostate Epithelial Cells

In normal prostate cells, cell membrane receptors are located within signalling microdomains called caveolae. During cancer progression, caveolae are lost and sequestered receptors move out onto lipid rafts. The aim of this study was to investigate whether a change in the localisation of receptors out of caveolae and onto the cell membrane increased cell proliferation invitro, and to determine whether this is related to changes in the cell signalling pathways. Normal human prostate epithelial cells (PrEC) and androgen-independent (PC3) cancer cells were cultured with 10nM dihydrotestosterone (DHT). The effects of oxytocin (OT) and gonadal steroids on proliferation were assessed using the MTS assay. Androgen receptor (AR) and oxytocin receptor (OTR) expression was identified by immunofluorescence and quantified by western blot. OTR and lipid raft staining was determined using Pearson’s correlation coefficient. Protein–protein interactions were detected and the cell signalling pathways identified. Treatment with OT did not affect the proliferation of PrEC. In PC3 cells, OT or androgen alone increased cell proliferation, but together had no effect. In normal cells, OTR localised to the membrane and AR localised to the nucleus, whereas in malignant cells both OTR and AR were identified in the cell membrane. Colocalisation of OTR and AR increased following treatment with androgens. Significantly fewer OTR/AR protein–protein interactions were seen in PrEC. With OT treatment, several cell signalling pathways were activated. Movement of OTR out of caveolae onto lipid rafts is accompanied by activation of alternative signal transduction pathways involved in stimulating increased cell proliferation.

scholarly journals Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hongzhen Li ◽  
Vijender Chaitankar ◽  
Jianqiong Zhu ◽  
Kyung Chin ◽  
Wenli Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Progenitor Cell ◽  
Sequencing Analysis ◽  
Normal Prostate ◽  
Prostate Epithelial Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

AbstractOlfactomedin 4 (OLFM4) is expressed in normal prostate epithelial cells and immortalized normal human prostate epithelial cells (RWPE1), but the identity of OLFM4-expressing cells within these populations and OLFM4’s physiological functions in these cells have not been elucidated. Using single-cell RNA sequencing analysis, we found here that OLFM4 was expressed in multiple stem/progenitor-like cell populations in both the normal prostate epithelium and RWPE1 cells and was frequently co-expressed with KRT13 and LY6D in RWPE1 cells. Functionally, OLFM4-knockout RWPE1 cells exhibited enhanced proliferation of the stem/progenitor-like cell population, shifts stem/progenitor-like cell division to favor symmetric division and differentiated into higher levels PSA expression cells in organoid assays compared with OLFM4-wild RWPE1 cells. Bulk-cell RNA sequencing analysis pinpointed that cMYC expression were enhanced in the OLFM4-knockout RWPE1 cells compared with OLFM4-wild cells. Molecular and signaling pathway studies revealed an increase in the WNT/APC/MYC signaling pathway gene signature, as well as that of MYC target genes that regulate multiple biological processes, in OLFM4-knockout RWPE1 cells. These findings indicated that OLFM4 is co-expressed with multiple stem/progenitor cell marker genes in prostate epithelial cells and acts as a novel mediator in prostate stem/progenitor cell proliferation and differentiation.

Expanded: a gene involved in the control of cell proliferation in imaginal discs

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1291-1301 ◽  
Author(s):  
M. Boedigheimer ◽  
A. Laughon
Keyword(s):  
Cell Proliferation ◽  
Protein Interactions ◽  
Essential Gene ◽  
Spontaneous Mutation ◽  
Growth Control ◽  
Imaginal Discs ◽  
Apical Surface ◽  
Protein Protein Interactions ◽  
Acid Protein ◽  
Disc Cells

The expanded gene was first identified by a spontaneous mutation that causes broad wings. We have identified an enhancer-trap insertion within expanded and used it to generate additional mutations, including one null allele. expanded is an essential gene, necessary for proper growth control of imaginal discs and, when mutant, causes either hyperplasia or degeneration depending on the disc. Wing overgrowth in expanded hypermorphs is limited to specific regions along the anterior-posterior and dorsal-ventral axis. expanded encodes a novel 1429 amino acid protein that is localized to the apical surface of disc cells and contains three potential SH3-binding sites. Together, these observations suggest that the Expanded protein engages in protein-protein interactions regulating cell proliferation in discs.

scholarly journals Proteolytic cleavage and truncation of NDRG1 in human prostate cancer cells, but not normal prostate epithelial cells

2013 ◽  
Vol 33 (3) ◽  
Author(s):  
Mohammad K. Ghalayini ◽  
Qihan Dong ◽  
Des R. Richardson ◽  
Stephen J. Assinder
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Western Blot ◽  
Cancer Cells ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Metastasis Suppressor ◽  
Normal Prostate ◽  
Truncated Protein ◽  
Prostate Epithelial Cells

NDRG1 (N-myc downstream regulated gene-1) is a metastasis suppressor that is down-regulated in prostate cancer. NDRG1 phosphorylation is associated with inhibition of metastasis and Western blots indicate two bands at ~41 and ~46 kDa. Previous investigations by others suggest the higher band is due to NDRG1 phosphorylation. However, the current study using a dephosphorylation assay and the Phos-tag (phosphate-binding tag) SDS/PAGE assay, demonstrated that the 46 kDa NDRG1 protein band was not due to phosphorylation. Further experiments showed that the NDRG1 protein bands were not affected upon glycosidase treatment, despite marked effects of these enzymes on the glycosylated protein, fetuin. Analysis using RT–PCR (reverse transcriptase–PCR) demonstrated only a single amplicon, and thus, the two bands could not result from an alternatively spliced NDRG1 transcript. Western-blot analysis of prostate cancer cell lysates identified the 41 kDa band to be a truncated form of NDRG1, with MS confirming the full and truncated proteins to be NDRG1. Significantly, this truncated protein was not present in normal human PrECs (prostate epithelial cells). Western-blot analysis using anti-NDRG1 raised to its N-terminal sequence failed to detect the truncated protein, suggesting that it lacked N-terminus amino acids (residues 1–49). Sequence analysis predicted a pseudotrypsin protease cleavage site between Cys49–Gly50. Such cleavage of NDRG1 in cancer cells may result in loss of NDRG1 tumour suppressive activity.

scholarly journals Insulin signalling: putting the G- in protein-protein interactions

2004 ◽  
Vol 380 (1) ◽  
pp. e11-e12 ◽  
Author(s):  
Craig C. MALBON
Keyword(s):  
Insulin Receptor ◽  
Cross Talk ◽  
Protein Interactions ◽  
Tyrosine Kinases ◽  
Cell Biology ◽  
Receptor Tyrosine Kinases ◽  
Insulin Signalling ◽  
Cell Signalling ◽  
Protein Protein Interactions ◽  
Proximal Point

Cell signalling via receptor tyrosine kinases, such as the insulin receptor, and via heterotrimeric G-proteins, such as Gαi, Gαs and Gαq family members, constitute two of most avidly studied paradigms in cell biology. That elements of these two populous signalling pathways must cross-talk to achieve proper signalling in the regulation of cell proliferation, differentiation and metabolism has been anticipated, but the evolution of our thinking and the analysis of such cross-talk have lagged behind the ever-expanding troupe of players and the recognition of multivalency as the rule, rather than the exception, in signalling biology. New insights have been provided by Kreuzer et al. in this issue of the Biochemical Journal, in which insulin is shown to provoke recruitment of Gαi-proteins to insulin-receptor-based complexes that can regulate the gain of insulin-receptor-catalysed autophosphorylation, a proximal point in the insulin-sensitive cascade of signalling. Understanding the convergence and cross-talk of signals from the receptor tyrosine kinases and G-protein-coupled receptor pathways in physical, spatial and temporal contexts will remain a major challenge of cell biology.

Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapies

2004 ◽  
Vol 108 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Ronan M. LONG ◽  
Colm MORRISSEY ◽  
John M. FITZPATRICK ◽  
R. William G. WATSON
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Prostate Gland ◽  
Western World ◽  
Cancer Therapies ◽  
Normal Prostate ◽  
Full Characterization ◽  
Prostate Epithelial Cells ◽  
Common Malignancy

Prostate cancer is the most common malignancy in males in the western world. However, little is known about its origin and development. This review highlights the biology of the normal prostate gland and the differentiation of basal epithelial cells to a secretory phenotype. Alterations in this differentiation process leading to cancer and androgen-independent disease are discussed, as well as a full characterization of prostate epithelial cells. A full understanding of the origin and characteristics of prostate cancer epithelial cells will be important if we are to develop therapeutic strategies to combat the heterogeneous nature of this disease.

scholarly journals Caspase- and Serine Protease-dependent Apoptosis by the Death Domain of FADD in Normal Epithelial Cells

2003 ◽  
Vol 14 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Jacqueline Thorburn ◽  
Laura M. Bender ◽  
Michael J. Morgan ◽  
Andrew Thorburn
Keyword(s):  
Epithelial Cells ◽  
Serine Protease ◽  
Death Domain ◽  
Cell Type ◽  
Normal Prostate ◽  
Effector Domain ◽  
Death Effector Domain ◽  
Prostate Epithelial Cells ◽  
Cell Type Specific ◽  
Death Effector

The adapter protein FADD consists of two protein interaction domains: a death domain and a death effector domain. The death domain binds to activated death receptors such as Fas, whereas the death effector domain binds to procaspase 8. An FADD mutant, which consists of only the death domain (FADD-DD), inhibits death receptor–induced apoptosis. FADD-DD can also activate a mechanistically distinct, cell type–specific apoptotic pathway that kills normal but not cancerous prostate epithelial cells. Here, we show that this apoptosis occurs through activation of caspases 9, 3, 6, and 7 and a serine protease. Simultaneous inhibition of caspases and serine proteases prevents FADD-DD–induced death. Inhibition of either pathway alone does not prevent cell death but does affect the morphology of the dying cells. Normal prostate epithelial cells require both the caspase and serine protease inhibitors to efficiently prevent apoptosis in response to TRAIL. In contrast, the serine protease inhibitor does not affect TRAIL-induced death in prostate tumor cells suggesting that the FADD-DD–dependent pathway can be activated by TRAIL. This apoptosis pathway is activated in a cell type–specific manner that is defective in cancer cells, suggesting that this pathway may be targeted during cancer development.

Protein-Protein Interactions in the Tetraspanin Web

Physiology ◽  
2005 ◽  
Vol 20 (4) ◽  
pp. 218-224 ◽  
Author(s):  
Shoshana Levy ◽  
Tsipi Shoham
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Protein Interactions ◽  
Membrane Microdomains ◽  
Protein Protein Interactions ◽  
Host Parasite Interactions ◽  
Evolutionarily Conserved ◽  
And Migration ◽  
Host Parasite ◽  
Partner Proteins

Tetraspanins are evolutionarily conserved membrane proteins that tend to associate laterally with one another and to cluster dynamically with numerous partner proteins in membrane microdomains. Consequently, members of this family are involved in the coordination of intracellular and intercellular processes, including signal transduction; cell proliferation, adhesion, and migration; cell fusion; and host-parasite interactions.

scholarly journals Network-Based Gene Expression Biomarkers for Cold and Heat Patterns of Rheumatoid Arthritis in Traditional Chinese Medicine

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Cheng Lu ◽  
Xuyan Niu ◽  
Cheng Xiao ◽  
Gao Chen ◽  
Qinglin Zha ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Cell Proliferation ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Protein Interactions ◽  
Acid Metabolism ◽  
Protein Protein Interactions ◽  
Significant Gene ◽  
Heat Pattern

In Traditional Chinese Medicine (TCM), patients with Rheumatoid Arthritis (RA) can be classified into two main patterns: cold-pattern and heat-pattern. This paper identified the network-based gene expression biomarkers for both cold- and heat-patterns of RA. Gene expression profilings of CD4+ T cells from cold-pattern RA patients, heat-pattern RA patients, and healthy volunteers were obtained using microarray. The differentially expressed genes and related networks were explored using DAVID, GeneSpring software, and the protein-protein interactions (PPI) method. EIF4A2, CCNT1, and IL7R, which were related to the up-regulation of cell proliferation and the Jak-STAT cascade, were significant gene biomarkers of the TCM cold pattern of RA. PRKAA1, HSPA8, and LSM6, which were related to fatty acid metabolism and the I-κB kinase/NF-κB cascade, were significant biomarkers of the TCM heat-pattern of RA. The network-based gene expression biomarkers for the TCM cold- and heat-patterns may be helpful for the further stratification of RA patients when deciding on interventions or clinical trials.

Sign in / Sign up

Export Citation Format

Share Document