caa a22 4500 445292660 CHVBK 20180317142533.0 cr unu---uuuuu 170323e20101201xx s 000 0 eng 10.1007/s11626-010-9353-8 doi (NATIONALLICENCE)springer-10.1007/s11626-010-9353-8 Modulation of TGF-β-inducible hypermotility by EGF and other factors in human prostate epithelial cells and keratinocytes [Elektronische Daten] [Wei Wei, Patricia Barron, James Rheinwald] 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 p16INK4A 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. The Society for In Vitro Biology, 2010 Prostate nationallicence Epithelial nationallicence Keratinocyte nationallicence Motility nationallicence TGF-beta nationallicence Laminin nationallicence EGF nationallicence Wei Wei Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital and Harvard Medical School, HIM 664, 77 Ave. Louis Pasteur, 02115, Boston, MA, USA aut Barron Patricia Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital and Harvard Medical School, HIM 664, 77 Ave. Louis Pasteur, 02115, Boston, MA, USA aut Rheinwald James Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital and Harvard Medical School, HIM 664, 77 Ave. Louis Pasteur, 02115, Boston, MA, USA aut In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/10(2010-12-01), 841-855 1071-2690 46:10<841 2010 46 11626 https://doi.org/10.1007/s11626-010-9353-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11626-010-9353-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wei Wei Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital and Harvard Medical School, HIM 664, 77 Ave. Louis Pasteur, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Barron Patricia Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital and Harvard Medical School, HIM 664, 77 Ave. Louis Pasteur, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Rheinwald James Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital and Harvard Medical School, HIM 664, 77 Ave. Louis Pasteur, 02115, Boston, MA, USA aut NATIONALLICENCE 773 0- In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/10(2010-12-01), 841-855 1071-2690 46:10<841 2010 46 11626 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer