%0 Journal Article
%~ PubMed
%A Hua, Sheng
%A Yao, Mu
%A Vignarajan, Soma
%A Witting, Paul
%A Hejazi, Leila
%A Gong, Zhen
%A Teng, Ying
%A Niknami, Marzieh
%A Assinder, Stephen
%A Richardson, Des
%A Dong, Qihan
%T Cytosolic phospholipase A2alpha sustains pAKT, pERK and AR levels in PTEN-null/mutated prostate cancer cells.
%B Biochimica et Biophysica Acta
%D 2013
%C Netherlands
%I Elsevier BV
%V 1831
%N 6
%P 1146-1157
%@ 0006-3002
%X 
%Z FOR Codes: 111201


%0 Journal Article
%~ PubMed
%A Dixon, K M
%A Lui, G Y L
%A Kovacevic, Z
%A Zhang, D
%A Yao, M
%A Chen, Z
%A Dong, Q
%A Assinder, S J
%A Richardson, D R
%T Dp44mT targets the AKT, TGF-β and ERK pathways via the metastasis suppressor NDRG1 in normal prostate epithelial cells and prostate cancer cells.
%B British Journal of Cancer
%D 2013
%C United Kingdom
%I Nature Publishing Group
%V 108
%N 2
%P 409-419
%@ 0007-0920
%X 
%Z FOR Codes: 60111 110199


%0 Journal Article
%~ PubMed
%A Bower, Neil I
%A Garcia de la Serrana, Daniel
%A Cole, Nicholas J
%A Hollway, Georgina E
%A Lee, Hung-Tai
%A Assinder, Stephen
%A Johnston, Ian A
%T STAC3 is required for myotube formation and myogenic differentiation in vertebrate skeletal muscle.
%B Journal of Biological Chemistry
%D 2012
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 287
%N 
%P 43936-43949
%@ 1083-351X
%X 
%Z FOR Codes: 304


%0 Journal Article
%~ PubMed
%A Assinder, Stephen
%A Cole, Nicholas
%T Does TGF-β induced formation of actin stress fibres reinforce Smad dependent TGF-β signalling in the prostate?
%B Medical hypotheses
%D 2011
%C United Kingdom
%I Churchill Livingstone
%V 76
%N 6
%P 802-4
%@ 1532-2777
%X In the normal prostate, and during early stages of prostate cancer (PCa) development, the cytokine transforming growth factor beta (TGF-??) acts as a tumour suppressor by inducing cytostasis and apoptosis. However, during tumour development these Smad signalling-dependent endpoints are lost in favour of Smad-independent tumourigenic actions of TGF-??. In this working hypothesis we present an argument for an intimate association between the TGF-?? signalling pathway and the actin cytoskeleton that acts to reinforce the tumour suppressive actions of TGF-?? in the normal prostate epithelial cell. The rationale is that TGF-?? induces expression of the actin binding and stabilising proteins transgelin and tropomyosin. Expression of these proteins is progressively repressed during PCa development, and is inhibited by constitutive activation of the Ras/MEK/ERK pathway, also known to antagonise TGF-?? tumour suppression in PCa. The subsequent de-stabilisation of the actin cytoskeleton might, therefore, result in suppression of TGF-??/Smad signalling as an intact link between cytoskeleton and TGF-?? receptor/Smad complex is essential. Filamin A is a scaffold protein that provides this link for receptor associated Smads. It is required for activation of the TGF-?? signal transduction pathway. Thus, actin filament disorganisation would prevent Filamin A/R-Smad mediated TGF-?? signalling, a subsequent loss of tumour suppression and hence promote the progression of PCa. Furthermore, it could be one mechanism by which the switch to a TGF-?? tumourigenic response occurs.
%Z FOR Codes: 60103 1112


%0 Journal Article
%A Assinder, Stephen
%T TAGLN (transgelin)
%B Atlas of Genetics and Cytogenetics in Oncology and Haematology
%D 2011
%C France
%I INstitut de l'Information Scientifique et Techniqu
%V 15
%N 6
%P 477-479
%@ 1768-3262
%X 
%Z FOR Codes: 60408


%0 Journal Article
%~ PubMed
%A Assinder, Stephen J
%A Au, Edith
%A Dong, Qihan
%A Winnick, Clare
%T A novel splice variant of the beta-tropomyosin (TPM2) gene in prostate cancer.
%B Molecular carcinogenesis
%D 2010
%C United States
%I John Wiley & Sons, Inc.
%V 49
%N 6
%P 525-31
%@ 1098-2744
%X Decreased expression of high molecular weight isoforms of tropomyosin (Tm) is associated with oncogenic transformation and is evident in cancers, with isoform Tm1 seemingly an important tumor suppressor. Tm1 expression in prostate cancer has not previously been described. In this study, while demonstrating suppressed levels of Tm1 in the prostate cancer cell lines LNCaP, PC3, and DU-145 compared to normal prostate epithelial cell primary isolates (PrEC), a novel splice variant of the TPM2 gene was identified. Quantitative RT-PCR determined significantly greater levels of the transcript variant in all three prostate cancer cell lines than in normal prostate epithelial cells. Characterization of this novel variant demonstrated it to include exon 6b, previously thought unique to the muscle-specific beta-Tm isoform, with an exon arrangement of 1-2-3-4-5-6a-6b-7-8-10. Inclusion of exon 6b introduces a premature stop codon directly following the 6a-6b exon boundary. Western blot analysis demonstrated the presence of a truncated protein in prostate cancer cell lines that was absent in normal prostate epithelial cells. It is hypothesized that this truncated protein will result in suppression of Tm1 polymer formation required for actin filament association. The lack of Tm polymer-actin association will result in loss of the stable actin microfilament organization and stress fiber formation, a state associated with cell transformation.
%Z FOR Codes: 60103 60112


%0 Journal Article
%~ PubMed
%A Prasad, Priya D
%A Stanton, Jo-Anne L
%A Assinder, Stephen J
%T Expression of the actin-associated protein transgelin (SM22) is decreased in prostate cancer.
%B Cell and tissue research
%D 2010
%C Germany
%I Springer
%V 339
%N 2
%P 337-47
%@ 1432-0878
%X Transgelin is an actin-binding protein shown to be tumour-suppressive. Loss of transgelin expression in transformed cells is associated with oncogenesis. This study aimed to determine whether transgelin expression was suppressed in prostate cancer. An in silico meta-analysis with public-domain expressed-sequence-tag libraries of normal human prostate epithelium, prostatic intraepithelial neoplasia, invasive carcinoma and metastasised lesions predicted decreased transgelin expression with disease progression. Similarly, analysis of Affymetrix gene chip data and the Oncomine database indicated that transgelin was one the 2% most significant of all down-regulated genes in response to prostate cancer. Analysis by quantitative reverse transcription with the polymerase chain reaction (qRT-PCR) of patient biopsies determined transgelin expression to be significantly lower in prostate tumour tissue than in matched normal tissue. Similarly, qRT-PCR and Western blot analysis of representative prostate cancer cell lines demonstrated significantly lower levels of transgelin mRNA and protein in all but the DU145 prostate cancer cell line. Increased expression of TAGLN and increased transgelin protein in response to treatment with transforming growth factor-beta suggested that reduced expression in prostate cancer was not attributable to gene promoter suppression by hypermethylation. Gene ontology function analysis highlighted the importance of transgelin in the co-deregulation of actin-binding proteins. Thus, transgelin is suppressed during prostate cancer progression and seems to be an important factor in the dysregulation of the actin cytoskeleton.
%Z FOR Codes: 60199 111201


%0 Journal Article
%~ PubMed
%A Tom, Nicole
%A Assinder, Stephen J
%T Oxytocin in health and disease.
%B The international journal of biochemistry & cell biology
%D 2010
%C United Kingdom
%I Pergamon
%V 42
%N 2
%P 202-5
%@ 1357-2725
%X Oxytocin is a nonapeptide of the neurohypophyseal protein family that binds specifically to the oxytocin receptor to produce a multitude of central and peripheral physiological responses. Within the central nervous system oxytocin is expressed by the neurons of the hypothalamus that project into higher brain centres and the posterior pituitary gland, from where it enters the circulation by release into the portal capillaries. Centrally, it modulates, maternal, sexual, social and stress related behaviour. Peripheral actions of oxytocin are commonly associated with smooth muscle contraction, particularly within the female and male reproductive tracts. Local synthesis of oxytocin along with its receptor in these regions indicates the presence of local oxytocinergic systems. More sinister implications for oxytocin in autism, depression and several cancers have recently been identified. A greater understanding of the role of oxytocinergic mechanisms will determine the potential for targeting this regulatory peptide in the pharmacological management of these disorders.
%Z FOR Codes: 60111 60103 60110


%0 Journal Article
%A Tom, Nicole C
%A Assinder, Stephen
%T Oxytocin: Recent developments
%B Biomolecular Concepts
%D 2010
%C Germany
%I Walter de Gruyter GmbH & Co. KG
%V 1
%N 5-6
%P 367-380
%@ 1868-5021
%X 
%Z FOR Codes: 60105


%0 Book Section
%A Assinder, Stephen
%T Oxytocin in the Pathophysiology of Prostate Cancer
%B Handbook of Oxytocin Research: Synthesis, Storage and Release, Actions and Drug Forms
%D 2009
%C United Kingdom
%I Nova Publishers
%V 
%N 
%P 155-170
%@ 9781608760237
%E Jastrow, Hugo
%E Feuerbach, Daniela
%X 
%Z FOR Codes: 60105 111201


%0 Journal Article
%~ PubMed
%A Assinder, Stephen J
%A Dong, Qihan
%A Mangs, Helena
%A Richardson, Des R
%T Pharmacological Targeting of the Integrated AKT, PTEN and TGF-{beta} Pathways in Prostate Cancer.
%B Molecular pharmacology
%D 2009
%C United States
%I Amer Soc Pharmacology Experimental Therapeutics
%V 75
%N 3
%P 429-36
%@ 0026-895X
%X Prostate cancer is a highly heterogenous disease in which a patient-tailored care program is much desired. Central to this goal is the development of novel targeted pharmacological interventions. To develop these treatment strategies, an understanding of the integration of cellular pathways involved in both tumorigenesis and tumor suppression is crucial. Of further interest are the events elicited by drug treatments that exploit the underlying molecular pathology in cancer. This review briefly describes the evidence that suggests integration of three established pathways: the tumorigenic phosphoinositide 3-kinase/protein kinase B (AKT) pathway, the tumor suppressive phosphatase and tensin homolog deleted on chromosome 10 pathway, and the tumor suppressive transforming growth factor-beta pathway. More importantly, we discuss novel pharmaceutical agents that target key points of integration in these three pathways. These new therapeutic strategies include the use of agents that target iron to inhibit proliferation via multiple mechanisms and suppression of AKT by cytosolic phospholipase A(2)-alpha inhibitors.
%Z FOR Codes: 111201


%0 Journal Article
%~ PubMed
%A Assinder, Stephen J
%A Dong, Qihan
%A Kovacevic, Zaklina
%A Richardson, Des R
%T The TGF-beta, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer.
%B Biochemical Journal
%D 2009
%C United Kingdom
%I Portland Press Ltd.
%V 417
%N 2
%P 411-421
%@ 1470-8728
%X A key to the development of improved pharmacological treatment strategies for cancer is an understanding of the integration of biochemical pathways involved in both tumorigenesis and cancer suppression. Furthermore, genetic markers that may predict the outcome of targeted pharmacological intervention in an individual are central to patient-focused treatment regimens rather than the traditional ''one size fits all'' approach. Prostate cancer is a highly heterogeneous disease in which a patient-tailored care program is a holy grail. This review will describe the evidence that demonstrates the integration of three established pathways: the tumour-suppressive TGF-beta (transforming growth factor-beta) pathway, the tumorigenic PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathway and the tumour-suppressive PTEN (phosphatase and tensin homologue deleted on chromosome 10) pathway. It will discuss gene polymorphisms and somatic mutations in relevant genes and highlight novel pharmaceutical agents that target key points in these integrated pathways.
%Z FOR Codes: 111201


%0 Journal Article
%~ PubMed
%A Assinder, Stephen J
%A Stanton, Jo-Ann L
%A Prasad, Priya D
%T Transgelin: An actin-binding protein and tumour suppressor.
%B The international journal of biochemistry & cell biology
%D 2009
%C United Kingdom
%I Pergamon
%V 41
%N 0
%P 482-6
%@ 1357-2725
%X Transgelin is a shape change sensitive 22 kDa actin-binding protein of the calponin family. It contains a C-terminal calponin-like module (CLIK(23)) and an upstream positively charged amino acid region required for actin binding. Transgelin is ubiquitous to vascular and visceral smooth muscle and is an early marker of smooth muscle differentiation, where its expression is driven by CArG box, smooth muscle gene promoter. It is also present in fibroblasts, and some epithelium where expression is likely driven by TGF-beta1. Transgelin null mice reveal that, whilst it is not required for smooth muscle development, transgelin may be involved in calcium-independent smooth muscle contraction. Recent evidence suggests that transgelin acts as a tumour suppressor. Its expression is lost in prostate, breast and colon cancers. This is consistent with suppression of the metallo matrix protease-9 (MMP-9) by transgelin, where MMP-9 is upregulated in these common cancers.
%Z FOR Codes: 1116


%0 Book Section
%A Nicholson, Helen
%A Assinder, Stephen
%T Male gametogenesis
%B Textbook of Assisted Reproduction
for Scientists in Reproductive Technology
%D 2008
%C Australia
%I VIVID Publishing
%V 
%N 
%P 3-30
%@ 9780980545913
%E Fleming, Steven
%E Cooke, Simon
%X 
%Z FOR Codes: 111404


%0 Journal Article
%~ PubMed
%A Assinder, Stephen
%A Davis, Ryan
%A Fenwick, Mark
%A Glover, Amy
%T Adult-only exposure of male rats to a diet of high phytoestrogen content increases apoptosis of meiotic and post-meiotic germ cells.
%B Reproduction
%D 2007
%C United Kingdom
%I BioScientifica Ltd.
%V 133
%N 1
%P 11-19
%@ 1470-1626
%X Apoptosis plays a critical role in regulating sperm production. Removal of androgens and gonadotropins, or estrogen administration induces germ cell apoptosis. It is hypothesized that dietary phytoestrogens increase apoptosis of developing germ cells, decreasing sperm production. This study aimed to test this in rats fed a high phytoestrogen diet only during adulthood. Male Wistar rats used in this study were offspring of females maintained on a low phytoestrogen diet prior to conception through to weaning. After weaning, juveniles were fed the same low phytoestrogen diet into adulthood. A cohort of males were transferred to a high phytoestrogen diet for 24 days and subsequently testes were collected from all animals. In the high phytoestrogen fed group, homogenization-resistant sperm counts were significantly decreased, as were epididymal sperm counts. Morphometric analysis determined round and elongated spermatid volumes to be significantly decreased, but seminiferous tubule lumen diameters to be significantly increased. TUNEL analysis determined that apoptosis of spermatocytes and round spermatids was significantly greater in the high phytoestrogen fed rats. Neither plasma gonadotropin concentrations nor testicular testosterone were altered. In conclusion, exposure of the adult male rat to a high phytoestrogen diet disrupts spermatogenesis, increasing germ cell apoptosis. This effect is independent of the hypothalamo-pituitary-testicular axis and is likely due to disruption of estrogen''s actions in the testis.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Assinder, S J
%T Oxytocin increases 5alpha-reductase activity of human prostate epithelial cells, but not stromal cells.
%B The Prostate
%D 2007
%C USA
%I John Wiley & Sons, Inc.
%V 68
%N 
%P 115-21
%@ 0270-4137
%X Oxytocin is known to modulate 5-alpha-reductase expression and has, therefore, been implicated in the etiology and novel pharmacological treatments of benign prostatic hyperplasia (BPH). These suggestions have been made in the absence of any direct evidence that oxytocin regulates expression or activity of 5-alpha-reductase isoenzymes in the human prostate. This study evaluated the effects of oxytocin on the activity and expression of 5-alpha-reductase isoenzymes I and II of human prostate stromal (PrSC; primary site of BPH development) and epithelial (PrEC) cells.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Whittington, Kate
%A Connors, Belinda
%A King, Keith
%A Assinder, Steve
%A Hogarth, Karole
%A Nicholson, Helen
%T The effect of oxytocin on cell proliferation in the human prostate is modulated by gonadal steroids: implications for benign prostatic hyperplasia and carcinoma of the prostate.
%B The Prostate
%D 2007
%C United States
%I John Wiley & Sons, Inc.
%V 67
%N 10
%P 1132-1142
%@ 0270-4137
%X BACKGROUND: Oxytocin (OT) is implicated in regulating prostate growth. OT concentrations are increased in benign, and decreased in malignant prostate disease. This study investigated whether the altered concentrations of OT present in prostate disease affect the proliferation of malignant and non-malignant human prostate cells. METHODS: The effects of varying concentrations of OT and gonadal steroids on cell proliferation of non-malignant prostatic epithelial (PrEC) and stromal (PrSC) cells and androgen dependent (LNCaP) and independent (PC-3) malignant cell lines were assessed. RESULTS: OT (>0.5 nmol . L(-1)) had no effect on PrEC proliferation when cells were cultured alone. When co-cultured with PrSC and gonadal steroids, OT inhibited epithelial cell proliferation. OT inhibited PrSC proliferation, when cells were cultured alone. When PrSC were co-cultured in the presence of estrogen physiological concentrations of OT were inhibitory. No effect on cell proliferation was observed with higher concentrations of OT. OT did not affect the proliferation of malignant cell lines in the absence of androgens but, in the presence of testosterone, low concentrations of OT (<1 nmol . L(-1)) stimulated proliferation of PC-3 cells. Disruption of caveolae in the plasma membrane removed the inhibitory effect of OT on PrSC proliferation but did not affect the stimulatory effect of OT on PC-3 cells cultured in the presence of androgens. CONCLUSIONS: Changes in prostatic concentrations of OT that occur with aging and malignant disease may act to facilitate cell proliferation. The localization of the OT receptor within the plasma membrane modulates OT''s proliferative response in the prostate. Prostate 67: 1132-1142, 2007. (c) 2007 Wiley-Liss, Inc.
%Z FOR Codes: