Role of ribosomal protein RPS2 in controlling let-7a expression in human prostate cancer.

We discovered that an inverse relationship exists in the expression of ras/c-myc and ribosomal protein RPS2 with pre-let-7a-1/let-7a/let-7f miRNA and prostate tumor cell malignancy. Nonmalignant IBC-10a cells expressed low levels of ras/RPS2 and elevated pre-let-7a-1/let-7a/let-7f miRNA, whereas the reverse occurred in malignant PCa-20a and PC-3ML cells. Stable transfection of IBC-10a cells with pBABE.

RPS2: a novel therapeutic target in prostate cancer.

Background: A number of studies have previously shown that the over expression of different ribosomal proteins might play an important role in cancer (i.e. S3a, L10, L16).

The ABCA5 protein: a urine diagnostic marker for prostatic intraepithelial neoplasia.

Purpose: To develop a urine diagnostic test for preneoplastic intraepithelial neoplasia of the prostate.

Experimental Design: We have used a DNA-binding assay and electrophoretic mobility shift assays (EMSA) to screen for novel duplexed DNA-binding sequences, which bind protein(s) overexpressed in crude protein extracts from high-grade prostatic intraepithelial neoplasia (HGPIN). EMSAs, immunohistochemistry, and ELISAs were used to measure expression of the ABCA5 protein identified as a specific marker in prostate tissue and patient urine.

Expression of a flt-4 (VEGFR3) splicing variant in primary human prostate tumors. VEGF D and flt-4t(Delta773-1081) overexpression is diagnostic for sentinel lymph node metastasis.

Utilizing a cDNA expression library established from human prostate PC-3ML tumor cells, we have cloned a truncated flt-4 gene, termed flt-4t(Delta773-1081). We have then utilized RNase protection and ELISA to measure the relative levels of VEGF B, C, D and flt-1, KDR, flt-4 and flt-4t(Delta773-1081) expression in freshly isolated benign prostatic hyperplasia or BPH tissue (n=21), primary prostate cancers (n=82) and matching sentinel lymph node metastases from stage T2a-T2b/T3 tumors (n=52). Comparisons of the primary tumors with BPH showed that there was a significant upregulation of VEGF-B (P=0.

Evidence for prostate cancer-associated diagnostic marker-1: immunohistochemistry and in situ hybridization studies.

Purpose: The purpose of this study was to characterize a novel gene/protein associated with prostate cancer, termed prostate cancer-associated diagnostic marker-1 [PCADM-1 (Hu Y, Wang M, Garcia FU, Aoyaki K, Stearns ME. Identification of PCADM-1 as a novel diagnostic marker for prostate cancer, submitted for publication)].

Experimental Design And Results: Immunological studies revealed that rabbit polyclonal antibodies generated against recombinant PCADM-1 specifically recognize the protein in crude protein extracts from a variety of prostate cancer cell lines (i.

Interleukin-10 activation of the interleukin-10E1 pathway and tissue inhibitor of metalloproteinase-1 expression is enhanced by proteasome inhibitors in primary prostate tumor lines.

The interleukin-10 (IL-10) activation of Janus kinase (JAK) family members (JAK1/TYK2) and IL-10E1 is subsequently inactivated by approximately 3-4 h in primary prostate tumor lines. We examined the effect of proteasome inhibition on IL-10 activation of the IL-10E1 pathway following stimulation of HPCA-10a cells. Treatment of HPCA-10a cells with the proteasome inhibitor, N-acetyl-L-leucinyl-L-leucinyl-norleucinal (LLnL), led to stable tyrosine phosphorylation of the IL-10 receptor and IL-10E1 following stimulation.

IL-10 signaling via IL-10E1 is dependent on tyrosine phosphorylation in the IL-10R alpha chain in human primary prostate cancer cell lines.

Interleukin 10 (IL-10) stimulates rapid nuclear translocation and binding of a 22 kDa protein, termed interleukin 10 enhancer 1 (IL-10E1), to a novel enhancer element (i.e. HTE-1) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) gene to upregulate TIMP-1 expression.

Interleukin 10 blocks matrix metalloproteinase-2 and membrane type 1-matrix metalloproteinase synthesis in primary human prostate tumor lines.

Insulin-like growth factor (IGF) I has been shown previously to up-regulate matrix metalloproteinase-2 (MMP-2) production, whereas the interleukin (IL) 10/IL-10 receptor axis has been found to down-regulate MMP-2 synthesis in tumor cells. In this paper, we showed that IL-10 activation of the IL-10 receptor blocked MMP-2 and membrane type 1 (MT1) -MMP transcription and protein synthesis in nonimmortalized primary human prostate cell strains (i.e.

IL-10/IL-10 receptor signaling regulates TIMP-1 expression in primary human prostate tumor lines.

An IL-10 responsive signal protein, termed IL-10E1, was cloned from human prostate cancer PC-3 ML cells based on its binding affinity for a novel enhancer element (i.e., HTE-1: 5'-CACGATGACTCATCACTGTTGAAAGACA-3') of the Tissue Inhibitor of metalloproteinase-1 (TIMP-1) gene.