Sehgal I, Powers S, Huntley B, Powis G, Pittelkow M, Maihle N J
Department of Biochemistry, Mayo Clinic, Rochester, MN 55905.
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4673-7. doi: 10.1073/pnas.91.11.4673.
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.
在进行治疗性激素剥夺后，前列腺癌细胞常常通过迄今尚未明确的机制发展出对雄激素不敏感的生长方式。神经肽先前已被认为是某些前列腺癌中的生长因子。在此，我们证明雄激素敏感的LNCaP人前列腺癌细胞在雄激素撤除后会产生并分泌神经降压素。我们表明，虽然LNCaP细胞表达神经降压素受体，但只有雄激素剥夺的细胞对外源性神经降压素表现出生长反应。我们进一步证明，由于雄激素诱导了一种对神经降压素具有活性的金属蛋白酶，雄激素刺激的细胞可能对外源性神经降压素不敏感。因此，缺乏雄激素的前列腺癌细胞发展出一种涉及神经降压素的替代性自分泌生长机制。
