Open AccessNeurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer.
Author(s) -
Inder Sehgal,
Stephen Powers,
Brenda K. Huntley,
Garth Powis,
Mark R. Pittelkow,
Nita J. Maihle
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.11.4673
Subject(s) - lncap , neurotensin , autocrine signalling , prostate cancer , endocrinology , medicine , androgen , androgen receptor , prostate , growth factor , biology , cancer research , cancer , hormone , neuropeptide , receptor
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.