Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0282612 (PIN)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously identified (M. Wang et al., Oncol. Res., in press, 1998) an enhancer element [human tissue inhibitor of metalloproteinase-1 enhancer-1 (HTE)] for the human tissue inhibitor of metalloproteinase-1 promoter that binds a novel zinc finger, cysteine-rich transcription factor (CRTF). In this study, we have used electrophoretic mobility shift assays to examine the relative level of expression of CRTF, jun/fos, and IFN-gamma responsive signal transducer activators of transcription (STATs) that bind specific HTE, activator protein, and IFN-gamma (Fcy and interferon regulatory factor) response motifs in tumor lines and human prostate tissue [i.e., normal (n = 3); benign prostatic hyperplasia (BPH; n = 12); high grade prostate intraepithelial neoplasia (PIN; n = 10); and prostate cancer adenocarcinoma (PCA; n = 61) plus seminal vesicle (n = 10) tissues]. The data showed that CRTF was overexpressed in PCA (Gleason's score, 10>8>6>5>4) compared with BPH, PIN, seminal vesicle, and normal tissues. To a much lesser degree, jun/fos and STAT 1 were also elevated in PCA compared to BPH, PIN, and normal tissues. In addition, blinded studies showed that CRTF and jun/fos were present at low levels in organ-confined specimens but at significantly elevated levels (P < 0.001) in samples exhibiting capsular penetration and localized spread, which indicated that CRTF and perhaps jun/fos were markers for cancer progression.
 ...
PMID:Specific transcription factors prognostic for prostate cancer progression. 974 34

Pituitary adenylate cyclase-activating peptide (PACAP), a cAMP-activating agent, is highly expressed in the hypothalamus during the period when many neuroendocrine cells become differentiated from the neural stem cells (NSCs). Activation of the cAMP system in rat hypothalamic NSCs differentiated these cells into beta-endorphin (BEP)-producing neurons in culture. When these in vitro differentiated neurons were transplanted into the paraventricular nucleus (PVN) of the hypothalamus of an adult rat, they integrated well with the surrounding cells and produced BEP and its precursor gene product, proopiomelanocortin (POMC). Animals with BEP cell transplants demonstrated remarkable protection against carcinogen induction of prostate cancer. Unlike carcinogen-treated animals with control cell transplants, rats with BEP cell transplants showed rare development of glandular hyperplasia, prostatic intraepithelial neoplasia (PIN), or well differentiated adenocarcinoma with invasion after N-methyl-N-nitrosourea (MNU) and testosterone treatments. Rats with the BEP neuron transplants showed increased natural killer (NK) cell cytolytic function in the spleens and peripheral blood mononuclear cells (PBMCs), elevated levels of antiinflammatory cytokine IFN-gamma, and decreased levels of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in plasma. These results identified a critical role for cAMP in the differentiation of BEP neurons and revealed a previously undescribed role of these neurons in combating the growth and progression of neoplastic conditions like prostate cancer, possibly by increasing the innate immune function and reducing the inflammatory milieu.
 ...
PMID:Cyclic adenosine monophosphate differentiated beta-endorphin neurons promote immune function and prevent prostate cancer growth. 1856 81

Acute viral infection of neurons presents a difficult problem to the host, since neurons are essential and not replaced, therefore cell-autonomous pathway(s) of suppressing viral replication are critical. We have examined the mechanisms by which neurons respond to exogenous interferons (IFNs) and observed that novel pathways inhibit acute vesicular stomatitis virus (VSV) replication. For both type I (IFN-beta) and Type II (IFN-gamma) interferons, post-translational modification of viral proteins contributed to the replication blockade, diminishing the efficiency of viral assembly and budding from the host neuron. IFN-gamma treatment induces the accumulation of NOS-1 in the absence of an increase of mRNA encoding this enzyme; a NOS-1-inhibiting protein, PIN, is rapidly ubiquitinated and eliminated in the presence of IFN-gamma. NOS-1 produces NO which combines with superoxide to form peroxynitrite (ONOO-), this binds tyrosines, cysteines, and serines; antagonism of NOS-1 with either non-specific or selective inhibitors block the antiviral effect of IFN-gamma. VSV proteins are decorated with -NO(2) in IFN-gamma-treated neurons, probably resulting in their diminished ability to interact properly and mature into budding virus. For IFN-beta, protein phosphorylation of the Matrix protein (M) and Phosphoprotein (P) were altered in infected neurons, with hyperphosphorylation of M (but not hypophosphorylated P) found in released virions. Hyperphosphorylated M protein does not immunoprecipitate with the viral ribonucleoprotein complex in IFN-beta-treated neurons. Thus both types of IFN interfere with viral assembly and release of infectious particles, but by distinct pathways.
 ...
PMID:DISTINCT MECHANISMS OF INHIBITION OF VSV REPLICATION IN NEURONS MEDIATED BY TYPE I AND TYPE II IFN. 2050 25