Document Detail

Modulation of TGF-β-inducible hypermotility by EGF and other factors in human prostate epithelial cells and keratinocytes.
MedLine Citation:
PMID:  21042878     Owner:  NLM     Status:  MEDLINE    
Keratinocytes migrating from a wound edge or initiating malignant invasion greatly increase their expression of the basement membrane protein Laminin-322 (Lam332). In culture, keratinocytes initiate sustained directional hypermotility when plated onto an incompletely processed form of Lam332 (Lam332') or when treated with transforming growth factor beta (TGF-β), an inducer of Lam332 expression. The development and tissue architecture of stratified squamous and prostate epithelia are very different, yet the basal cells of both express p63, α6β4 integrin, and Lam332. Keratinocytes and prostate epithelial cells grow well in nutritionally optimized culture media with pituitary extract and certain mitogens. We report that prostate epithelial cells display hypermotility responses indistinguishable from those of keratinocytes. Several culture medium variables attenuated TGF-β-induced hypermotility, including Ca(++), serum, and some pituitary extract preparations, without impairing growth, TGF-β growth inhibition, or hypermotility on Lam322'. Distinct from its role as a mitogen, EGF proved to be a required cofactor for TGF-β-induced hypermotility and could not be replaced by HGF or KGF. Prostate epithelial cells have a short replicative lifespan, restricted both by p16(INK4A) and telomere-related mechanisms. We immortalized the normal prostate epithelial cell line HPrE-1 by transduction to express bmi1 and TERT. Prostate epithelial cells lose expression of p63, β4 integrin, and Lam332 when they transform to invasive carcinoma. In contrast, HPrE-1/bmi1/TERT cells retained expression of these proteins and normal TGF-β signaling and hypermotility for >100 doublings. Thus, keratinocytes and prostate epithelial cells possess common hypermotility and senescence mechanisms and immortalized prostate cell lines can be engineered using defined methods to yield cells retaining normal properties.
Wei Wei; Patricia D Barron; James G Rheinwald
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-02
Journal Detail:
Title:  In vitro cellular & developmental biology. Animal     Volume:  46     ISSN:  1543-706X     ISO Abbreviation:  In Vitro Cell. Dev. Biol. Anim.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-02     Completed Date:  2011-03-16     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9418515     Medline TA:  In Vitro Cell Dev Biol Anim     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  841-55     Citation Subset:  IM    
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital and Harvard Medical School, 77 Ave. Louis Pasteur, Boston, MA 02115, USA.
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MeSH Terms
Blotting, Western
Cell Adhesion Molecules / metabolism
Cell Culture Techniques / methods*
Cell Movement / physiology*
Epidermal Growth Factor / metabolism*
Epithelial Cells / metabolism,  physiology*
Keratinocytes / metabolism,  physiology*
Prostate / cytology*
Transduction, Genetic
Transforming Growth Factor beta / metabolism*
Grant Support
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Transforming Growth Factor beta; 0/kalinin; 62229-50-9/Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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