Expression of gamma-aminobutyric acid receptor (subtype A) in prostate cancer.

Background: In prostate cancer, gamma-aminobutyric acid (GABA) has been previously reported to increase cellular proliferation via the ionotropic GABAa receptor (GABAar) and to promote cellular invasiveness via the metabotropic GABAb receptor.

Methods: In this study, we have investigated, by immunohistochemistry, GABAar levels in 12 normal human prostate, 13 benign prostatic hyperplasia (BPH) and 148 human prostate cancer specimens. We have also examined the effect of several GABA agonists and antagonists on the in vitro proliferation of four human prostate cancer cell lines: LNCaP, MDA-PCA-2b, DU145 and PC3.

Ryanodine receptor expression correlates with tumor grade in breast cancer.

Ryanodine receptors (RyRs) have been previously implicated in the proliferation of human T-lymphocytes and melanocytes as well as in the motility of astrocytes. We have examined RyR expression in 57 ductal, human breast cancer specimens, by immunohistochemistry. Moderate to high RyR immunostaining was found in 47 (82%) of the specimens.

Reduced Kv1.3 potassium channel expression in human prostate cancer.

The presence of Kv1.3 voltage-gated potassium channels in rat and human prostate epithelial cells has been previously reported. We examined, by immunohistochemistry, Kv1.

N-methyl-D-aspartate receptor in human prostate cancer.

Expression of the N-methyl-D-aspartate receptor (NMDAr) and its involvement in cellular proliferation is well-known in tumors of neuronal tissue, such as glioma and neuroblastoma. We have investigated NMDAr expression in the normal, hyperplastic and neoplastic human prostate by immunohistochemistry. Low stromal NMDAr immunostaining was observed in 2 of 12 (17%) normal prostate specimens, but epithelial NMDAr staining was not seen.

Potentiation of the antiproliferative activity of MKT-077 by loperamide, diltiazem and tamoxifen.

MKT-077, a delocalized lipophilic cation, selectively targets cancer cells. MKT-077 has been reported to inhibit the growth of several tumor types and has undergone phase I clinical testing. We have examined the effect of MKT-077, alone and in combination with the antidiarrheal drug loperamide.