Linked Life Data

15580310

Source:http://linkedlifedata.com/resource/pubmed/id/15580310

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-1-20
pubmed:abstractText
Human WWOX gene encodes a proapoptotic WW domain-containing oxidoreductase WOX1 (also named WWOX, FOR2 or WWOXv1). Apoptotic and stress stimuli activate WOX1 via Tyr33 phosphorylation and nuclear translocation. WOX1 possesses a tetrad NSYK motif in the C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, which may bind estrogen and androgen. Here, we determined that 17beta-estradiol (E(2)) activated WOX1, p53 and ERK in COS7 fibroblasts, primary lung epithelial cells, and androgen receptor (AR)-negative prostate DU145 cells, but not in estrogen receptor (ER)-positive breast MCF7 cells. Androgen also activated WOX1 in the AR-negative DU145 cells. These observations suggest that sex hormone-mediated Tyr33 phosphorylation and nuclear translocation of WOX1 is independent of ER and AR. Stress stimuli increase physical binding of p53 with WOX1 in vivo. We determined here that E(2) increased the formation of p53/WOX1 complex and their nuclear translocation in COS7 cells; however, nuclear translocation of this complex could not occur in MCF7 cells. By immunohistochemistry, we determined that progression of prostate from normal to hyperplasia, cancerous and metastatic stages positively correlate with upregulation and activation of WOX1 and WOX2 (FOR1/WWOXv2). In contrast, breast cancer development to a premetastatic state is associated with upregulation and Tyr33 phosphorylation of cytosolic WOX1 and WOX2, followed by significant downregulation or absent expression during metastasis. These Tyr33-phosphorylated proteins are mostly located in the mitochondria without translocating to the nuclei, which is comparable to those findings in cultured breast cancer cells. Together, sex steroid hormone-induced activation of WOX1 and WOX2 is independent of ER and AR, and this activation positively correlates with cancerous progression of prostate and breast to a premetastatic state.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
714-23
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15580310-Animals, pubmed-meshheading:15580310-Breast Neoplasms, pubmed-meshheading:15580310-Cell Line, pubmed-meshheading:15580310-Cercopithecus aethiops, pubmed-meshheading:15580310-Disease Progression, pubmed-meshheading:15580310-Estradiol, pubmed-meshheading:15580310-Humans, pubmed-meshheading:15580310-Hyperplasia, pubmed-meshheading:15580310-Male, pubmed-meshheading:15580310-Mice, pubmed-meshheading:15580310-Mitochondria, pubmed-meshheading:15580310-Neoplasm Metastasis, pubmed-meshheading:15580310-Oxidoreductases, pubmed-meshheading:15580310-Phosphorylation, pubmed-meshheading:15580310-Prostatic Neoplasms, pubmed-meshheading:15580310-Protein Binding, pubmed-meshheading:15580310-Protein Transport, pubmed-meshheading:15580310-Receptors, Androgen, pubmed-meshheading:15580310-Tumor Suppressor Protein p53, pubmed-meshheading:15580310-Tumor Suppressor Proteins, pubmed-meshheading:15580310-Tyrosine, pubmed-meshheading:15580310-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
17beta-Estradiol upregulates and activates WOX1/WWOXv1 and WOX2/WWOXv2 in vitro: potential role in cancerous progression of breast and prostate to a premetastatic state in vivo.
pubmed:affiliation
Guthrie Research Institute, Laboratory of Molecular Immunology, 1 Guthrie Square, Sayre, PA 18840, USA. chang_nanshan@guthrie.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't