title: Generation of active TGF-beta by prostatic cell cocultures using novel basal and luminal prostatic epithelial cell lines.
abstract: Two prostatic epithelial lines, one of basal origin and one of luminal origin, were established from the dorsolateral prostates of p53 null mice. The cell lines are nontumorigenic when inoculated subcutaneously under the renal capsule or intraprostatically in syngeneic mice. The luminal cell line (PE-L-1) expresses cytokeratins 8 and 18 and the basal cell line (PE-B-1) expresses cytokeratins 5 and 14. The basal cells require serum for growth, whereas the luminal cells grow only in serum-free medium. Both cell lines require the presence of growth factors for optimal growth in culture, with EGF and FGF-2 having the greatest effect on the growth rate. Both lines express androgen receptor (AR) mRNA and protein. Androgen stimulates growth of the basal cell line, indicating that the ARs are functional, whereas growth of the luminal cells is unaffected by androgens. The luminal line is significantly inhibited by exogenous TGF-beta and produces low levels of endogenous TGF-beta. In contrast, the basal cell line produces significant amounts of TGF-beta and its growth is not influenced by this cytokine. Coculture of luminal cells with prostatic smooth muscle cells results in the generation of increased levels of biologically active TGF-beta, indicating a paracrine mechanism of TGF-beta activation that may be involved in the maintenance of normal prostatic function. To our knowledge this is the first report describing both basal and luminal prostatic cell lines from a single inbred animal species and the first indication that prostatic epithelial and stromal cells interact to generate the biologically active form of TGF-beta. These lines will provide an important model for determining basal/luminal interactions in both in vitro and in vivo assays.
authors.affiliation: Department of Cell Biology and Kaplan Cancer Center, New York University School of Medicine, New York, New York, USA. salms01@endeavor.med.nyu.edu
authors.forename: S N
authors.initials: SN
authors.lastname: Salm
authors.forename: Y
authors.initials: Y
authors.lastname: Koikawa
authors.forename: V
authors.initials: V
authors.lastname: Ogilvie
authors.forename: A
authors.initials: A
authors.lastname: Tsujimura
authors.forename: S
authors.initials: S
authors.lastname: Coetzee
authors.forename: D
authors.initials: D
authors.lastname: Moscatelli
authors.forename: E
authors.initials: E
authors.lastname: Moore
authors.forename: H
authors.initials: H
authors.lastname: Lepor
authors.forename: E
authors.initials: E
authors.lastname: Shapiro
authors.forename: T T
authors.initials: TT
authors.lastname: Sun
authors.forename: E L
authors.initials: EL
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001681:Biological Assay; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D018920:Coculture Techniques; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D016158:Genes, p53; D006133:Growth Substances / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007633:Keratins / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000494:pharmacology
chemical_list: D006133:Growth Substances; D007328:Insulin; D011944:Receptors, Androgen; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007633:Keratins; D002772:Cholera Toxin; D006854:Hydrocortisone