Disease relevance of APRIN

• Polymorphism and allelic loss at the AS3 locus on 13q12-13 in esophageal squamous cell carcinoma [1].

High impact information on APRIN

• We mapped the complete BRCA2 deletion, which extends over at least 298 kb and showed that it does not affect APRIN/AS3, previously characterized as a tumor suppressor gene, but it comprises several loci corresponding to proven or putative transcripts of unknown functional significance [2].
• Recently, we reported that the AS3 protein mediates the androgen-induced quiescence in androgen-target human cell lines [3].
• Mechanism of androgen action on cell proliferation: AS3 protein as a mediator of proliferative arrest in the rat prostate [3].
• S9 cells expressing a tetracycline-regulated sense AS3 were also used [3].
• The AS3 protein was not expressed in cells that incorporate bromodeoxyuridine [3].

Biological context of APRIN

• Two ODNs, AS1 and AS3, were found to reduce mRNA expression by 40-50%, as determined by reverse transcription polymerase chain reaction [4].
• These results suggest that polymorphic variation and LOH at the AS3 locus might be associated with lymph node involvement in ESC [1].
• Although polymorphisms were found in exon 10 and introns 21, 23, 25 and 29, a possible tumor specific mutation in exon 6 was identified in only one of 31 ESC-derived cell lines, indicating that the remaining allele of AS3 was rarely inactivated by mutational events [1].
• Sequence analysis revealed that the patients had novel mutations, one nonsense mutation (AS1 (C613X)) and three single base changes leading to amino acid substitutions (AS2 (L321F), AS3 (I274V), and AS4 (M719I)) [5].
• Conclusion: AS3 transfection increases MCF-7 cell apoptosis induced by 5 Gy-radiation, and this mechanism may be closely associated with abrogation of G(1 ) phase arrest [6].

Anatomical context of APRIN

• These data suggest that AS3 is a mediator of the proliferative arrest in the normal rat prostate in situ and human prostate cell lines and that its expression is androgen-induced [3].
• AS3 was expressed in the nuclei of over 90% of the epithelial cells and about 40% of the smooth muscle cells of the intact rat prostate [3].
• One of these new genes, AS3, shows high expression in the early regulatory phase of androgen-induced proliferative shutoff in the cell variants and in the prostates of castrated rats [7].

Associations of APRIN with chemical compounds

• Moreover, Casodex reduces induction of AS3 by 1,25(OH)2D3 suggesting that it is a candidate for the Casodex effect [8].
• The compound 2-(N'-2-pentylidene-hydrazino)-3-phenyl-3H-quinazolin-4-one (AS3) showed more potent anti-inflammatory activity when compared to the reference standard diclofenac sodium [9].
• In contrast there was only a small bias on the measurements of a Drager PM8060 and a Datex AS3 compact monitor, which was statistically significant (oxygen and desflurane) but clinically irrelevant [10].

Analytical, diagnostic and therapeutic context of APRIN

• We therefore examined AS3 alterations by PCR-SSCP and RT-PCR [1].

References