Highly tumorigenic human androgen receptor-positive prostate cancer cells overexpress angiogenin.

We have recently established a highly tumorigenic cell line, LNCaP-CR, derived from human androgen-dependent prostate cancer LNCaP cells. In the present study, we examined the genes responsible for the high tumorigenicity of LNCaP-CR cells. The cDNA microarray analysis and protein array of secreted factors indicated angiogenin (ANG), an angiogenic factor, as a candidate gene.

Establishment of a highly tumorigenic LNCaP cell line having inflammatory cytokine resistance.

Human androgen-dependent prostate cancer LNCaP cells are low tumorigenic even in immunodeficient mice and were killed by the synergistic effect of inflammatory cytokines, IL-beta and IL-6. To establish a highly tumorigenic LNCaP cell line, we isolated the cytokine-resistant LNCaP-CR cell line and examined the phenotypes. The parental LNCaP cells were induced to commit apoptosis by the addition of IL-1beta and IL-6, but LNCaP-CR cells showed strong resistance against the cytokine action.

Prevention of neomycin-induced nephrotoxic event in pig proximal tubular epithelial cell line by apolipoprotein E3.

Nephrotoxicity is one of critical problems of aminoglycoside antibiotics. We examined the protective effect of apolipoprotein E3 (apoE3), one of ligands for megalin, on neomycin-induced extracellular release of lactate dehydrogenase, a marker of cell necrosis using pig proximal tubular LLC-PK1 cells. Neomycin significantly induced the extracellular release of lactate dehydrogenase, but apoE3 successfully suppressed it.

Apolipoprotein E3 (apoE3) safeguards pig proximal tubular LLC-PK1 cells against reduction in SGLT1 activity induced by gentamicin C.

Megalin, a family of endocytic receptors related to the low-density lipoprotein (LDL) receptor, is a major pathway for proximal tubular aminoglycoside accumulation. We previously reported that aminoglycoside antibiotics reduce SGLT1-dependent glucose transport in pig proximal tubular epithelial LLC-PK1 cells in parallel with the order of their nephrotoxicity. In this study, using a model of gentamicin C (GMC)-induced reduction in SGLT1 activity, we examined whether ligands for megalin protect LLC-PK1 cells from the GMC-induced reduction in SGLT1 activity.

Ectopic expression of the amino-terminal peptide of androgen receptor leads to androgen receptor dysfunction and inhibition of androgen receptor-mediated prostate cancer growth.

Androgen receptor (AR) is a ligand-activated transcription factor that requires androgen binding to initiate a series of molecular events leading to specific gene activation. AR has been suggested to form an antiparallel homodimer based on the characteristics of high affinity interaction between the amino (N) and carboxyl (C) termini of it. Recently, it is suggested that AR N-to-C interaction is critical for the ability of this receptor to up-regulate the transcription of androgen-responsive genes, and may be a new target for treatment of prostate cancer (PCa).

Aminoglycoside antibiotics reduce glucose reabsorption in kidney through down-regulation of SGLT1.

Nephrotoxicity is known to be a major clinical side effect of aminoglycoside antibiotics. Aminoglycosides cause damage to proximal tubular cells in kidney, however the mechanism of toxicity is still unclear. In order to elucidate the mechanism of nephrotoxicity, we studied the effect of aminoglycoside antibiotics on glucose transport systems in vitro and in vivo.