title: Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer.
abstract: After therapeutic hormone deprivation, prostate cancer cells often develop androgen-insensitive growth through mechanisms thus far undefined. Neuropeptides have been previously implicated as growth factors in some prostate cancers. Here, we demonstrate that androgen-sensitive LNCaP human prostate cancer cells produce and secrete neurotensin following androgen withdrawal. We show that while LNCaP cells express the neurotensin receptor, only androgen-deprived cells exhibit a growth response to exogenous neurotensin. We further demonstrate that androgen-stimulated cells may be refractory to exogenous neurotensin due to androgen induction of a metalloprotease active toward neurotensin. Thus, prostate cancer cells deprived of androgen develop an alternative autocrine growth mechanism involving neurotensin.
authors.affiliation: Department of Biochemistry, Mayo Clinic, Rochester, MN 55905.
authors.forename: I
authors.initials: I
authors.lastname: Sehgal
authors.forename: S
authors.initials: S
authors.lastname: Powers
authors.forename: B
authors.initials: B
authors.lastname: Huntley
authors.forename: G
authors.initials: G
authors.lastname: Powis
authors.forename: M
authors.initials: M
authors.lastname: Pittelkow
authors.forename: N J
authors.initials: NJ
authors.lastname: Maihle
mesh_terms: D000728:Androgens / Q000378:metabolism*; D002455:Cell Division; D010450:Endopeptidases / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D008297:Male; D009496:Neurotensin / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D018028:Receptors, Neurotensin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D006133:Growth Substances; D018028:Receptors, Neurotensin; D009496:Neurotensin; D010450:Endopeptidases