Disease relevance of PINX1

• The expression of PINX1, a possible telomerase inhibitor and a putative tumor suppressor, has not been studied in human cancers, including gastric cancer (GC) [1].
• Mutational analysis of PINX1 in hereditary prostate cancer [2].
• METHODS: The entire coding sequence of LPTS gene was examined for mutations by single strand conformation polymorphism (SSCP) assay and PCR products direct sequencing in 56 liver cancer cell lines, 7 ovarian cancer and 7 head neck tumor cell lines and 70 pairs of HCC tissues samples [3].
• VMHx hamsters underwent accelerated gonadal recrudescence compared to Pinx and Sham hamsters [4].
• Compared to sham subordinates, pinx subordinates experienced adrenal enlargment and twofold greater wounding and had lighter thymus glands and final body weights [5].

High impact information on PINX1

• Loss of heterozygosity and histone hypoacetylation of the PINX1 gene are associated with reduced expression in gastric carcinoma [1].
• Expression of PINX1 in a GC cell line, MKN-74, was induced by treatment with trichostatin A (TSA) or nicotinamide (NAM) [1].
• Chromatin immunoprecipitation assay of MKN-74 cells revealed that acetylation of histone H4 in the 5' untranslated region (UTR) of PINX1 was enhanced by treatment with TSA or NAM, whereas acetylation of histone H3 was not changed by TSA or NAM [1].
• We examined expression of PINX1 by quantitative reverse transcription (RT)-PCR in 73 cases of GC, and 45 of these cases were further studied for loss of heterozygosity (LOH) by PCR with microsatellite marker D8S277 [1].
• Recently, we found that plasma homocysteine (Hcy) levels are increased in pinealectomized (PINX) rats and melatonin reverses this increase [6].

Biological context of PINX1

• Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1 and reduces the telomere length [7].
• AIM: To find the point mutations meaningful for inactivation of liver-related putative tumor suppressor gene (LPTS) gene, a human novel liver-related putative tumor suppressor gene and telomerase inhibitor in hepatocellular carcinoma [3].
• Cloning and characterization of the promoter region of human LPTS/PinX1 gene [8].
• The gene for LPTS/PinX1 encodes a potent telomerase inhibitor and suppresses tumor cell growth [8].
• The effects of lesions (x) of the suprachiasmatic nucleus (SCN) or paraventricular nucleus (PVN), or pinealectomy (PINX) on gonadal recrudescence, body and fat pad weights, and food intake were examined in photoregressed male Siberian hamsters (Phodopus sungorus sungorus) [9].

Anatomical context of PINX1

• To test whether the ventromedial hypothalamus is necessary to maintain reproductive quiescence once testicular regression has been achieved, photoregressed male hamsters were subjected to lesions of the ventromedial hypothalamus (VMHx), pinealectomy (Pinx), or sham operation (Sham) [4].
• CB tests over an 8-week period following surgery indicated that copulatory impairments developed in all animals, but deficits occurred more rapidly among short photoperiod males with intact pineal glands (SP-SHAM PINX), compared to pinealectomized males housed in either the long (LP-PINX) or short photoperiod (SP-PINX) [10].

Associations of PINX1 with chemical compounds

• Treatment with propranolol or isoproterenol did not have any effect on convulsive activity of PINX gerbils, except that isoproterenol increased the excitability of all the gerbils [11].
• Although declines in cortical and hypothalamic norepinephrine content were found after alpha-methylparatyrosine (alpha MPT) or PINX, treatment with alpha MPT did not produce convulsions in SHAM gerbils or in gerbils which were PINX one week earlier [11].
• Ten days after emergence, PINX animals either had a disrupted/abnormal melatonin cycle and were non-courters or had a cycle similar to SHAM males and courted [12].

Physical interactions of PINX1

• MCRS2 interacts with LPTS/PinX1 in vitro, in vivo and colocalizes with LPTS/PinX1 in cells [7].

Regulatory relationships of PINX1

• Variation in Pinx1 expression may be a reaction induced by hTERT expression variation [13].

Other interactions of PINX1

• To explore the proteins that might be involved in the telomerase pathway, we performed a yeast two-hybrid screening with LPTS/PinX1 as the bait [7].
• Pinx1 mRNA expression was tightly correlated with telomerase reverse transcriptase (hTERT) mRNA expression during differentiation [13].

Analytical, diagnostic and therapeutic context of PINX1

• We measured serum leptin and melatonin levels by ELISA in (a) intact and pinealectomized (pinx) male hamsters kept under long daylight conditions [14 h of light (14L)]; (b) intact and pinx hamsters under short daylight (10L); and (c) intact hamsters in constant light (24L) [14].

References