Disease relevance of AIG1

• Androgen-induced redox changes in prostate cancer cells: what are causes and effects [1]?
• Androgen-induced hepatoma [2].
• The reversibility and long term significance of androgen-induced stimulation of CPV and, in particular, its relationship to the onset and severity of benign prostatic hyperplasia remain to be clarified [3].
• For example, androgen-induced prevalence of loss of libido or vigor increased below testosterone concentrations of 15 nmol/liter (P < 0.001), whereas depression and diabetes mellitus type 2 (also in nonobese men) were significantly more present in men with testosterone concentrations below 10 nmol/liter (P < 0.001) [4].
• The clinical repercussions of mutations in CYP19 on the fetal-placental unit have highlighted the major role of placental aromatase in the protection of the female fetus from androgen excess, thus preventing androgen-induced pseudohermaphrodism and virilization of the mother [5].

Psychiatry related information on AIG1

• We conclude that androgen-induced changes in Na+ current inactivation are not mediated by PKA and suggest that PKA-mediated increases in Na+ current underlie increases in the amplitude of the electric organ discharge observed in social interactions or with changes in water conductance [6].

High impact information on AIG1

• Here we report that the major and persistent DDT metabolite, p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has little ability to bind the oestrogen receptor, but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in developing, pubertal and adult male rats [7].
• Antioxidant vitamins C plus E blocked both androgen-induced DNA-binding activity and production of reactive oxygen species [8].
• Androgen-induced recruitment of RNA polymerase II to a nuclear receptor-p160 coactivator complex [9].
• Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor [10].
• Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells [11].

Chemical compound and disease context of AIG1

• Androgen-induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA [12].
• The DDT1 MF2 smooth muscle cell line was derived from an estrogen/androgen-induced leiomyosarcoma arising in the hamster ductus deferens [13].
• ErbB1 and prostate cancer: ErbB1 activity is essential for androgen-induced proliferation and protection from the apoptotic effects of LY294002 [14].
• The antiandrogenic activity was corroborated by the inhibition of androgen-induced prostate hypertrophy in orchiectomized rats through the use of testosterone, testosterone propionate, dihydrotestosterone, androstenedione, and dehydroepiandrosterone [15].
• We investigated the role of androgen-induced oxidative stress in prostate cancer using the androgen-responsive LNCaP human prostate cancer cell line exposed to a 1-nM concentration of the synthetic androgen R1881 (which correlates with serum androgen levels) [16].

Biological context of AIG1

• The IMAP/IAN family of AIG1-like GTPases is conserved among vertebrates and angiosperm plants and has been postulated to regulate apoptosis, particularly in context with diseases such as cancer, diabetes, and infections [17].
• Vector-driven expression of antisense-AS3 blocked the induction of androgen-induced endogenous AS3 mRNA and blocked the inhibitory effect of androgens on cell proliferation [18].
• Potential mediators of this androgen-induced proliferative shutoff were identified by means of subtracted cDNA libraries [18].
• Conversely, downregulation of endogenous Daxx expression by RNA interference enhances androgen-induced prostate-specific antigen expression in LNCaP cells [19].
• Moreover, androgen-induced IGF-IR up-regulation involves the activation of the Src-extracellular signal-regulated kinase pathway, because it was inhibited by both the Src inhibitor PP2 and the MEK-1 inhibitor PD98059 [20].

Anatomical context of AIG1

• AIG1 mRNA was expressed at a relatively high level in the heart, ovary, testis, liver, and kidney [21].
• Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells [22].
• RNA interference and oocyte maturation studies suggested that androgen-induced maturation was mediated in part by the XeAR in a transcription-independent fashion, perhaps by altering G protein-mediated signaling [23].
• Furthermore, the 114-kDa androgen-induced phosphorylated AR protein band was not detectable in genital skin fibroblasts [24].
• BXL-628 counteracted keratinocyte growth factor (KGF) and androgen-induced cell proliferation and stimulated apoptosis with a parallel reduced expression of the survival oncoprotein Bcl-2 [25].

Associations of AIG1 with chemical compounds

• Further study will be needed to understand the functions of AIG1 in the androgen-regulated hair cycle [21].
• Similarly, coumarin significantly inhibited the androgen-induced increase in prostatic size when administered to castrated rats receiving testosterone [26].
• Furthermore, calreticulin antisense oligonucleotide reverses the androgen-induced resistance to A23187 in LNCaP cells [27].
• Hydroxyflutamide acted as a true antiandrogen since it lacked agonist activity and was an inhibitor of androgen-induced transcriptional activation [28].
• Androgen-induced NH2- and COOH-terminal Interaction Inhibits p160 coactivator recruitment by activation function 2 [29].

Physical interactions of AIG1

• Some AR LBD mutations do not affect ligand binding but they disrupt androgen-induced interaction of the N-terminal motif FXXLF and C-terminal activation function 2 (AF2) [30].

Regulatory relationships of AIG1

• Overexpression of AP-1 (jun and fos proteins) also inhibited androgen-induced PSA promoter activity [31].
• Mutagenesis of the basic amino acid Arg(537) in the protease cleavage region, as suggested by mass spectrometry, abrogated both the androgen-induced accumulation of the 60-kDa product and decrease in cell death induced by FKHR, suggesting that the residue Arg(537) is a potential protease cleavage site [32].
• p53 represses androgen-induced transactivation of prostate-specific antigen by disrupting hAR amino- to carboxyl-terminal interaction [33].
• This finding indicates that the coactivation function of c-Jun is sufficient for regulating androgen-induced growth of LNCaP cells. c-Jun also enhances AR transactivtion in androgen-independent LNCaP cells, which closely mimic hormone-refractory prostate cancer cells in gene expression and growth behavior [34].
• These observations suggest that MIS regulates androgen-induced gene expression and growth in prostate cancer cells through a NFkappaB-dependent but Smad1-independent mechanism [35].

Other interactions of AIG1

• Neither N-terminal truncated nor proline-rich region-deleted AR mutants, which are unable to bind to p85alpha and Src, respectively, was able to mediate androgen-induced PI3K/Akt activation [36].
• On the one hand, PTEN and an inhibitor of phosphoinositide 3-kinase repressed the transcriptional activity of the AR as well as androgen-induced cell proliferation and production of prostate-specific antigen [37].
• Progression of LNCaP prostate tumor cells during androgen deprivation: hormone-independent growth, repression of proliferation by androgen, and role for p27Kip1 in androgen-induced cell cycle arrest [38].
• Therefore, the androgen-induced secretory protein AGR2 may serve as a potential therapeutic target and/or molecular marker for prostate cancer [39].
• This resulted in transient activation of CDK2 activity, but was insufficient to override the androgen-induced G1 block [40].

Analytical, diagnostic and therapeutic context of AIG1

• In a Northern blot analysis, the major 1.5 kb and minor 1.2 kb bands of AIG1 mRNA were detected [21].
• Using fluorescence imaging with green fluorescent protein androgen receptor and Western blot analysis, we demonstrated that DIM inhibited androgen-induced androgen receptor (AR) translocation into the nucleus [41].
• Depot gonadotropin-releasing hormone agonist blunts the androgen-induced suppression of spermatogenesis in a clinical trial of male contraception [42].
• Both microarray and quantitative RT-PCR analyses demonstrated marked induction of the human prostate overexpressed protein 1 (PTOV1) gene by testosterone in the cell lines: this gene was recently identified as a novel androgen-induced gene involved in prostate tumour cell proliferation [43].
• Because it is independent of body size and gestational age, the anogenital ratio should be useful in diagnosing androgen-induced labioscrotal fusion in both premature and full-term female infants [44].

References