Distinct patterns of endothelin axis expression in primary prostate cancer.

Objectives: Emerging evidence supports a role for endothelin-1 (ET-1), endothelin A and B receptors (ET(A) and ET(B), respectively), and neutral endopeptidase (NEP) in the progression of prostate carcinoma. In clinical trials for advanced prostate cancer, ET axis blockade significantly delayed the time to disease progression in a subset of patients. We examined ET axis expression in prostate cancer, prostatic intraepithelial neoplasia, and normal adjacent tissue and then analyzed the relationship of the protein levels with disease progression.

Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops.

The biologic effects of endothelin-1 (ET-1) are not limited to its potent vasoconstricting activity. The endothelin receptors, ETA and ETB, have differential tissue and functional distributions. Here we showed that dendritic cells (DCs), the major antigen-presenting cells in the adaptive limb of the immune system, produce large amounts of ET-1 and significantly increase the expression of endothelin receptors upon maturation.

Endothelin A receptor blockade does not alter PSA secretion in prostate cancer cell lines.

Background: Some men treated with atrasentan (ABT-627), an endothelin A (ETA) receptor inhibitor, had declines in their serum PSA levels. It is our hypothesis that this decrease is due to anti-tumoral activity and not a reduction in PSA secretion at the cellular level.

Methods: Two PSA secreting prostate cancer cell lines (LAPC4 and LNCaP) were treated with atrasentan and an ETB receptor antagonist (A192621) in varying concentrations (10(-6)-10(-10) M) and PSA levels were measured in the culture media.

Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model.

Background: Fatty acid synthase (FAS) is the major enzyme required to convert carbohydrates to fatty acids. Recent evidence suggests that FAS activity is essential for prostate cancer growth and survival, since blocking the enzyme activity results in cell death. In this study, the role of FAS up-regulation during prostate tumor progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model was investigated.