Membrane metalloendopeptidase suppresses prostate carcinogenesis by attenuating effects of gastrin-releasing peptide on stem/progenitor cells.

Aberrant neuroendocrine signaling is frequent yet poorly understood feature of prostate cancers. Membrane metalloendopeptidase (MME) is responsible for the catalytic inactivation of neuropeptide substrates, and is downregulated in nearly 50% of prostate cancers. However its role in prostate carcinogenesis, including formation of castration-resistant prostate carcinomas, remains uncertain.

Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening.

Background: MYC family members are among the most frequently deregulated oncogenes in human cancers, yet direct therapeutic targeting of MYC in cancer has been challenging thus far. Synthetic lethality provides an opportunity for therapeutic intervention of MYC-driven cancers.

Methods: A pooled kinase shRNA library screen was performed and next-generation deep sequencing efforts identified that PRKDC was synthetically lethal in cells overexpressing MYC.

Detection and organ-specific ablation of neuroendocrine cells by synaptophysin locus-based BAC cassette in transgenic mice.

The role of cells of the diffuse neuroendocrine system in development and maintenance of individual organs and tissues remains poorly understood. Here we identify a regulatory region sufficient for accurate in vivo expression of synaptophysin (SYP), a common marker of neuroendocrine differentiation, and report generation of Tg(Syp-EGFP(loxP)-DTA)147(Ayn) (SypELDTA) mice suitable for flexible organ-specific ablation of neuroendocrine cells. These mice express EGFP and diphtheria toxin fragment A (DTA) in SYP positive cells before and after Cre-loxP mediated recombination, respectively.

MET-dependent cancer invasion may be preprogrammed by early alterations of p53-regulated feedforward loop and triggered by stromal cell-derived HGF.

MET, a receptor protein tyrosine kinase activated by hepatocyte growth factor (HGF), is a crucial determinant of metastatic progression. Recently, we have identified p53 as an important regulator of MET-dependent cell motility and invasion. This regulation occurs via feedforward loop suppressing MET expression by miR-34-dependent and -independent mechanisms.

Selenite triggers rapid transcriptional activation of p53, and p53-mediated apoptosis in prostate cancer cells: Implication for the treatment of early-stage prostate cancer.

Supra-nutritional selenium supplementation has emerged as an attractive new approach to intervene in a range of human cancers, in particular prostate cancer. However, scanty information is currently available on molecular mechanisms underlying selenium's anticancer action. The tumor suppressor p53 plays an important role in preventing transformation by transcriptional regulation of a range of genes that are involved in vital cell functions such as DNA repair, cell cycle arrest, and induction of apoptosis.

Pro-neural transcription factors as cancer markers.

Background: The aberrant transcription in cancer of genes normally associated with embryonic tissue differentiation at various organ sites may be a hallmark of tumour progression. For example, neuroendocrine differentiation is found more commonly in cancers destined to progress, including prostate and lung. We sought to identify proteins which are involved in neuroendocrine differentiation and differentially expressed in aggressive/metastatic tumours.

Core-shell silica nanoparticles as fluorescent labels for nanomedicine.

Progress in biomedical imaging depends on the development of probes that combine low toxicity with high sensitivity, resolution, and stability. Toward that end, a new class of highly fluorescent core-shell silica nanoparticles with narrow size distributions and enhanced photostability, known as C dots, provide an appealing alternative to quantum dots. Here, C dots are evaluated with a particular emphasis on in-vivo applications in cancer biology.

Cell lineage-specific interactions between Men1 and Rb in neuroendocrine neoplasia.

Inactivation of multiple endocrine neoplasia (MEN) type 1 gene (Men1) results in development of multiple endocrine tumors in Men1(+/-) mice and in humans. Intriguingly, loss of the wild-type retinoblastoma 1 (Rb) gene also leads to MEN-like phenotype in Rb(+/-) mice. To evaluate potential genetic interactions between these genes, we prepared and characterized Men1(+/-)Rb(+/-) compound mice in parallel with their parental genotypes.

Mouse models of prostate adenocarcinoma with the capacity to monitor spontaneous carcinogenesis by bioluminescence or fluorescence.

The application of Cre/loxP technology has resulted in a new generation of conditional mouse models of prostate cancer. Here, we describe the improvement of the conditional Pten deletion model of prostate adenocarcinoma by combining it with either a conditional luciferase or enhanced green fluorescent protein reporter line. In these models, the recombination mechanism that inactivates the Pten alleles also activates the reporter gene.

Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of prostatic ducts.

Recently, we have shown that prostate epithelium-specific deficiency for p53 and Rb tumor suppressors leads to metastatic cancer, exhibiting features of both luminal and neuroendocrine differentiation. Using stage-by-stage evaluation of carcinogenesis in this model, we report that all malignant neoplasms arise from the proximal region of the prostatic ducts, the compartment highly enriched for prostatic stem/progenitor cells. In close similarity to reported properties of prostatic stem cells, the cells of the earliest neoplastic lesions express stem cell marker stem cell antigen 1 and are not sensitive to androgen withdrawal.

A novel full-length gene of human ribosomal protein L14.22 related to human glioma.

Background: This study was undertaken to obtain differentially expressed genes related to human glioma by cDNA microarray and the characterization of a novel full-length gene.

Methods: Total RNA was extracted form human glioma and normal brain tissue, and mRNA was used as a probe. The results of hybridization procedure were scanned with the computer system.

Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer.

Pathways mediated by p53 and Rb are frequently altered in aggressive human cancers, including prostate carcinoma. To test directly the roles of p53 and Rb in prostate carcinogenesis, we have conditionally inactivated these genes in the prostate epithelium of the mouse. Inactivation of either p53 or Rb leads to prostatic intraepithelial neoplasia developing from the luminal epithelium by 600 days of age.

[Tumor relevance analysis of a highly conserved gene by using gene microarray hybridization].

Preliminary function research of a highly conserved human gene,which was cloned from human fetal cDNA library during large-scale cDNA sequencing,is illustrated in this article. Bioinformatics analysis indicates that this gene is highly conserved in human, mouse, fruit fly, thaliana and fission yeast. Other bioinformatics analysis implies its relevance with tumors.

cDNA microarray in isolation of novel differentially expressed genes related to human glioma and clone of a novel full-length gene.

Background: This investigation was undertaken to obtain differentially expressed genes related to human glioma using cDNA microarray and the characterization of one novel full-length gene.

Methods: Total RNA was extracted from human glioma tissues and normal brain tissues, and mRNA was used to make probes. After hybridization and washing, the results were scanned using a computer system.

Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb+/- mice.

Mice with a single copy of the retinoblastoma gene (Rb(+/-)) develop a syndrome of multiple neuroendocrine neoplasia. They usually succumb to fast-growing, Rb-deficient melanotroph tumors of the pituitary intermediate lobe, which are extremely rare in humans. Thus, full assessment of Rb role in other, more relevant to human pathology, neoplasms is complicated.

Isolation of novel differentially expressed genes related to human glioma using cDNA microarray and characterizations of two novel full-length genes.

Identification of the genes that are differentially expressed between brain tumor and normal brain tissues is important for understanding the molecular basis of these nerve system tumors and for defining possible targets for therapeutic intervention. This investigation is intended to obtain differentially expressed genes related to human glioma using cDNA microarray. Total RNA was extracted from human glioma specimens and normal brain tissues, and mRNA was obtained by oligotex chromatography.

Cloning and characterization of ARHGAP12, a novel human rhoGAP gene.

Rho GTPase activating proteins (GAPs) stimulate the intrinsic GTP hydrolysis activity of Rho family proteins. Here we report the cloning of two splice variants of a novel gene named ARHGAP12 (access number), which has an ORF of 2541bp. Profilescan search result showed that its putative protein contains five domains: rhoGAP, SH3, PH and two WW domains.

Cloning, expression and characterisation of a human Nudix hydrolase specific for adenosine 5'-diphosphoribose (ADP-ribose).

The human NUDT9 gene has been mapped to 4q22 and shown to give rise to two alternatively spliced mRNAs, NUDT9alpha and NUDT9beta, that encode a member of the Nudix hydrolase family. Both transcripts were readily detected in heart and skeletal muscle and also in liver, kidney and pancreas. NUDT9alpha protein was expressed in Escherichia coli and shown specifically to hydrolyse ADP-ribose and IDP-ribose to the corresponding nucleoside 5'-monophosphates and ribose 5-phosphate.

Identification and characterization of AGTRAP, a human homolog of murine Angiotensin II Receptor-Associated Protein (Agtrap).

Several classes of cytoplasmic proteins have been found to interact specifically with the carboxyl-terminal cytoplasmic region of the angiotensin II type 1 (AT(1)) receptor to regulate different aspects of AT(1) receptor physiology. The murine Angiotensin II Receptor-Associated Protein (Agtrap) is a new member of them. We have recently cloned a new human gene cDNA that codes for a homolog of the murine Agtrap protein from a human fetal brain cDNA library.

Cloning and characterization of a novel human transcription factor AP-2 beta like gene (TFAP2BL1).

The AP-2 transcription factor has been shown to play an important role in development, morphogenesis, apoptosis, cell-cycle control and has also been implicated in mammary oncogenesis. Here we report the cloning and characterization of a novel human transcription factor AP-2 like gene (TFAP2BL1), which is located on human chromosome 6p12.1-21.