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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-1-27
pubmed:abstractText
The prostate is one of the most abundant sources of nerve growth factor (NGF) outside of the nervous system. NGF is a member of the neurotrophin family of growth factors which in mammals also includes brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). These neurotrophins can bind with high affinity to a family of tropomyosin receptor kinases (trks). These receptors are trkA, which binds NGF; trkB, which binds both BDNF and NT-4/5; and trkC, which binds NT-3. In order to characterize the molecular expression of the neurotrophins and their corresponding trk receptors in the prostate we performed Northern blot analysis for the neurotrophins and reverse transcription-polymerase chain reaction (RT-PCR) coupled with Southern blot analysis for the trk family of receptors on smooth muscle stromal cells from the prostate, the androgen responsive LNCaP prostate tumor cell line and the androgen refractory TSU-pr1 prostate tumor cell line. The results show that smooth muscle stromal cells expressed NGF, BDNF and trkC, whereas both epithelial cell lines expressed trkA, trkB and trkC to various degrees. NT-3 was not detected in either the smooth muscle stromal cells or in both epithelial cell lines. This suggests that the stromal cell derived NGF and BDNF may interact via paracrine mechanisms with trkA and trkB receptors, respectively, on the adjacent epithelial cells. Interestingly, the androgen responsive LNCaP cell line did not express any of the neurotrophins, whereas the androgen refractory TSU-pr1 cell line expressed NGF, BDNF and NT-4/5. This suggests that the autocrine expression of NGF, BDNF and NT-4/5 is up-regulated in prostate epithelial cells following their transformation to an androgen refractory pathology. Hence, the malignant transformation of prostate epithelial tumor cells may facilitate their escape from a paracrine dependence on stromal cell derived neurotrophins by the acquisition of the autocrine expression of neurotrophins. Since the pathology of malignant cell migration within the prostate is predominantly by direct extension around prostatic nerves the upregulation of autocrine neurotrophin expression within prostate epithelial tumor cells may be concomitant with transformation to a malignant phenotype capable of invasion along the perineural space and extracapsular metastasis to distant sites of tumor formation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0303-7207
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
134
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15-22
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Molecular characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial and stromal cells of the human prostate.
pubmed:affiliation
Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.