Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-22
pubmed:abstractText
Clinical and experimental studies have suggested that estrogens, the archetype of female hormones, participate in the control of male germ cell proliferation and that fetal exposure to environmental estrogens may contribute to hypofertility and/or to testicular germ cell cancer. However, the underlying mechanisms remain to be elucidated. 17beta-Estradiol (E2) conjugated to BSA was able to stimulate human testicular seminoma cell proliferation by triggering a rapid, nongenomic, membrane-mediated activation of ERK1/2 and cAMP-dependent protein kinase A (PKA). Both ERK1/2 and PKA participated in this promoting effect. This activation was associated with phosphorylation of the transcription factor cAMP response element-binding protein and the nuclear factor retinoblastoma protein. Enhanced proliferation together with ERK activation could be reversed by pertussis toxin, a G protein inhibitor. Estrogen receptors (ERs) in JKT-1 were characterized by immunofluorescence, subcellular fractioning, and Western blot. JKT-1 cells did not express ERalpha but ERbeta, which localized to the mitochondria and the nucleus but not to the membrane. Moreover, neither ICI-182,780, a classical ER antagonist, nor tamoxifen, a selective ER modulator, could reverse the 17beta-estradiol-BSA-induced promoting effect. Estrogens contribute to human testicular germ cell cancer proliferation by rapid activation of ERK1/2 and PKA through a membrane nonclassical ER. This nongenomic effect represents a new basis for understanding the estrogenic control of spermatogenesis and evaluating the role of fetal exposure to xenoestrogens during malignant transformation of testicular germ stem cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
149
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
565-73
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18039775-Adult, pubmed-meshheading:18039775-Cell Cycle, pubmed-meshheading:18039775-Cell Division, pubmed-meshheading:18039775-Cell Line, Tumor, pubmed-meshheading:18039775-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:18039775-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:18039775-Estradiol, pubmed-meshheading:18039775-GTP-Binding Protein alpha Subunits, Gi-Go, pubmed-meshheading:18039775-Humans, pubmed-meshheading:18039775-MAP Kinase Signaling System, pubmed-meshheading:18039775-Male, pubmed-meshheading:18039775-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:18039775-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:18039775-Phosphorylation, pubmed-meshheading:18039775-Retinoblastoma Protein, pubmed-meshheading:18039775-Seminoma, pubmed-meshheading:18039775-Serum Albumin, Bovine, pubmed-meshheading:18039775-Testicular Neoplasms
pubmed:year
2008
pubmed:articleTitle
Estrogens promote human testicular germ cell cancer through a membrane-mediated activation of extracellular regulated kinase and protein kinase A.
pubmed:affiliation
Unité Mixte de Recherche Institut National de la Santé et de la Recherche Médicale Unité 670 Faculty of Medicine of Nice, 06102, Nice Cedex 02, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't