Disease relevance of Tinagl

• Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia [1].
• In gel shift assays, the recombinant DNA-binding domain displays an affinity for a fragment of the long terminal repeat of mouse mammary tumor virus and for an intronic fragment of the gene coding for the C3 component of the androgen-regulated rat prostatic binding protein [2].
• In a major urinary protein (MUP)-promoter/simian virus 40 (SV40)Tag transgenic mouse line (MT-D2) the liver-directed, androgen-regulated transgene expression leads to synchronized pathology resulting in a stepwise progression to multiple hepatocellular carcinomas [3].
• FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells [4].
• In castrated animals, a single, low, environmentally relevant dose of cadmium (20 microg/kg body weight) increased the wet weight of the prostate (1.97- to 3-fold) and the seminal vesicle complex (approximately 1.5-fold) and increased the expression of the androgen-regulated gene, probasin (27-fold) [5].

High impact information on Tinagl

• Despite this difference in the androgenic regulation of integrated C3 rat genes, both type of cell lines still demonstrated androgen-regulated growth characteristics [6].
• This study establishes gamma-8 as a critical protein for basal AMPA receptor expression and localization at extrasynaptic sites in the hippocampus and raises the possibility that TARP-dependent control of AMPA receptors during synapse development and plasticity may be widespread [7].
• In brain regions that express multiple isoforms, such as cerebral cortex, TARP-AMPA receptor complexes are strictly segregated, suggesting distinct roles for TARP isoforms [8].
• Expression of the homeobox gene Pem, which is androgen-regulated in SC, was severely decreased [9].
• Arg-1, Gly-2, Val-4, Gln-6, and Gly-7 of the peptide were identified as putative TCR contact residues by testing the peptide analogs for their capacity to sensitize targets for VSV-specific cytolytic T-lymphocyte clones [10].

Chemical compound and disease context of Tinagl

• We observed subsequently that trp-p8 is lost in the transition to androgen independence in a prostate cancer xenograft model and in prostate cancer tissue from patients treated preoperatively with antiandrogen therapy, suggesting that trp-p8 is androgen regulated, and its loss may be associated with more advanced disease [11].

Biological context of Tinagl

• The cloned 2.0-kb sized Arg1 cDNA encoded 414 amino acid sequences [12].
• This might have been due to the replacement of the cysteinyl active site for proteinase to serine residue in the Arg1 amino acid sequences [12].
• DNA sequence polymorphism in an androgen-regulated gene is associated with alteration in the encoded RNAs [13].
• Furthermore, data on binding of truncated peptides show that, although the Arg-1 side chain has been assigned as a TCR contact residue, the main-chain atoms of the N-terminal amino group are most likely involved in interacting with the major histocompatibility complex molecule [10].
• Therefore, in the absence of testicular androgens, NE secretions were sufficient to maintain LNCaP cell growth and androgen-regulated gene expression in vivo [14].

Anatomical context of Tinagl

• Here we report isolation of an androgen-regulated novel gene from an androgen-dependent mouse mammary Shionogi carcinoma SC-3 cell line [12].
• Tmprss2 encodes an androgen-regulated type II transmembrane serine protease (TTSP) expressed highly in normal prostate epithelium and has been implicated in prostate carcinogenesis [15].
• These data provide the first demonstration of a stromal-specific AR coactivator that has an effect on an androgen-regulated growth factor that is essential for stromal/epithelial cell communication in the prostate [16].
• A 5-kilobase pair promoter fragment of the murine epididymal retinoic acid-binding protein gene drives the tissue-specific, cell-specific, and androgen-regulated expression of a foreign gene in the epididymis of transgenic mice [17].
• Identification of a functional androgen response element in the promoter of the gene for the androgen-regulated aldose reductase-like protein specific to the mouse vas deferens [18].

Associations of Tinagl with chemical compounds

• Isolation of an androgen-inducible novel lipocalin gene, Arg1, from androgen-dependent mouse mammary Shionogi carcinoma cells [12].
• Androgen-regulated ornithine decarboxylase mRNAs of mouse kidney [19].
• Intron and 5'-flanking regions of the androgen-regulated C3 subunit gene contain potential cis-acting transcription control sequences including several 15-base pair (bp) partial palindromes resembling response elements for glucocorticoid (GRE) and progesterone (PRE) receptors [20].
• Northern blot analysis of RNA from intact, castrate, or testosterone-replaced epididymides confirmed that these mitochondrial mRNAs as well as the rRNA were androgen regulated with a 2- to 5-fold reduction in expression observed after 4 weeks castration with partial to full recovery to precastrate levels upon 4 weeks of testosterone replacement [21].
• Prostate-specific antigen expression was assessed to determine the effect of ZD6474 on androgen-regulated genes [22].

Physical interactions of Tinagl

• Functional analysis and androgen-regulated expression of mouse organic anion transporting polypeptide 1 (Oatp1) in the kidney [23].

Regulatory relationships of Tinagl

• Clonal lines with different levels of AZ-1 expression were established from Y-1 adrenocortical cells that originally express Cyp11b-1 but little AZ-1 [24].
• The homeodomain-containing transcription factor NKX3.1 is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner [25].
• A murine epididymal retinoic-acid-binding protein (mE-RABP) is specifically expressed in the mid/distal caput epididymidis and is androgen regulated [26].
• The nucleotide sequence of MpSv-1, a novel androgen-regulated gene exclusively expressed in mouse seminal vesicle, was analyzed to establish a 5'-flanking region of 2123 bp, three exons of 95, 765, and 330 bp, and two introns of 222 and 811 bp [27].

Other interactions of Tinagl

• Analyses of the clonal lines revealed that Cyp11b-1 is detected in the clonal lines maintaining little AZ-1 expression and becomes undetectable in those expressing AZ-1 [24].
• On the other hand, irrespective of the AZ-1 expression, all clones expressed cholesterol side-chain cleavage enzyme, which occurs throughout the cortical zones [24].
• Three genes with a pattern closely resembling that of Pem, a prototypical androgen-regulated gene expressed in Sertoli cells, were selected for confirmation by quantitative RT-PCR and additional analysis [28].
• The role of forkhead box A2 to restrict androgen-regulated gene expression of lipocalin 5 in the mouse epididymis [29].
• Androgen regulated expression of a spermine binding protein gene in mouse ventral prostate [30].

Analytical, diagnostic and therapeutic context of Tinagl

• In Northern blotting, Arg1 mRNA was found in kidney, heart, lung, and to a lesser degree, in spleen and liver [12].
• Furthermore, DNA-protein complex immunoprecipitation assays reveal that HDAC4 is recruited to an androgen-regulated promoter through ARR19 [31].
• Northern blot and in situ hybridization analyses demonstrated that IGFBP-5 is androgen-regulated in CWR22 [32].
• Identification of androgen-regulated genes in mouse kidney by representational difference analysis and random arbitrarily primed polymerase chain reaction [33].
• To distinguish the direct effects of androgens on this cell type, DNA microarrays were used to identify androgen-regulated genes in the mouse proximal caput epididymidis (PC-1) cell line [34].

References