Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
1993-12-1
pubmed:abstractText
Normal human keratinocytes synthesize and secrete biologically active nerve growth factor (NGF) in a growth regulated fashion (Di Marco, E., Marchisio, P. C., Bondanza, S., Franzi, A. T., Cancedda, R., and De Luca, M. (1991) J. Biol. Chem. 266, 21718-21722). Here we show that the same human keratinocytes bind NGF via low and high affinity receptors. In parallel with the course of NGF synthesis, the expression of low affinity NGF receptor (p75NGFr) decreases when a confluent, differentiated, and fully stratified epithelium is obtained. In skin sections, p75NGFr is present in basal keratinocytes and absent from suprabasal, terminally differentiated cells. The trkA protooncogene product (p140trkA), a component of the NGF receptor, is not expressed by keratinocytes. Instead, keratinocytes express a new member of the trk family (that we termed trkE), which generates 3.9-kilobase transcripts. Keratinocyte-derived NGF plays a key role in the autocrine epidermal cell proliferation. This has been proven by (i) direct effect of NGF on [3H]thymidine incorporation, (ii) inhibition of autocrine keratinocyte growth by monoclonal antibodies (alpha D11) inhibiting human NGF biological activity, and (iii) inhibition of autocrine keratinocyte proliferation by a trk-specific inhibitor, the natural alkaloid K252a. These data provide evidence that NGF, in addition to its effect as a survival and differentiation factor, is a potent regulator of cell proliferation, at least in human epithelial cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22838-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7693679-3T3 Cells, pubmed-meshheading:7693679-Animals, pubmed-meshheading:7693679-Base Sequence, pubmed-meshheading:7693679-Cell Division, pubmed-meshheading:7693679-Cells, Cultured, pubmed-meshheading:7693679-DNA Primers, pubmed-meshheading:7693679-Epidermis, pubmed-meshheading:7693679-Epithelial Cells, pubmed-meshheading:7693679-Epithelium, pubmed-meshheading:7693679-Humans, pubmed-meshheading:7693679-Keratinocytes, pubmed-meshheading:7693679-Kinetics, pubmed-meshheading:7693679-Mice, pubmed-meshheading:7693679-Molecular Sequence Data, pubmed-meshheading:7693679-Nerve Growth Factors, pubmed-meshheading:7693679-Polymerase Chain Reaction, pubmed-meshheading:7693679-RNA, pubmed-meshheading:7693679-Receptors, Nerve Growth Factor, pubmed-meshheading:7693679-Thymidine, pubmed-meshheading:7693679-Tritium
pubmed:year
1993
pubmed:articleTitle
Nerve growth factor binds to normal human keratinocytes through high and low affinity receptors and stimulates their growth by a novel autocrine loop.
pubmed:affiliation
Laboratorio di Differenziamento Cellulare, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't