Disease relevance of PITX1

• Restoration of PITX1 in the colon cancer cells inhibited tumorigenicity in a wild-type RAS-dependent manner [1].
• In contrast, PITX1 mRNA expression is decreased in Barrett's esophagus, compared with matching normal squamous esophagus specimens, and is further decreased in Barrett's-associated cancer [2].
• Thus, there was no relationship between Ptx1 expression and a particular type of pituitary adenomas [3].
• Modulation of interferon expression by hepatitis C virus NS5A protein and human homeodomain protein PTX1 [4].
• Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation [5].

Psychiatry related information on PITX1

• Of these, 14 families underwent a psycho-educative intervention programme called BFT (Behavioural Family Therapy) [6].

High impact information on PITX1

• Thus, PITX1 suppresses tumorigenicity by downregulating the RAS pathway through RASAL1 [1].
• Interestingly, we observed low expression of PITX1 in prostate and bladder tumors and in colon cancer cell lines containing wild-type RAS [1].
• REST is a transcriptional repressor that silences neuron-specific gene expression, and PITX1 is a homeodomain transcription factor that promotes the expression of a negative regulator of Ras [7].
• Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity [8].
• Ptx1 (Pitx1) is a bicoid-related homeobox transcription factor expressed from the onset of pituitary development [9].

Chemical compound and disease context of PITX1

• Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial cells [10].
• Inhibitors of endosomal and Golgi trafficking (NH4Cl and brefeldin A) prevented the intoxication of HT29/C1 cells by Clostridium difficile toxin A and cholera toxin, respectively, but not by BFT [11].
• Furthermore, SB203580 prevented BFT-induced colitis in the mouse ileum, as evidenced by significant decreases in villous destruction, neutrophil infiltration, and mucosal congestion [12].

Biological context of PITX1

• Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett's esophagus and Barrett's-associated adenocarcinoma [2].
• Using in vitro binding assays and a series of site-specific mutations of the proximal hPRL promoter, we mapped the B1 and B2 bicoid sites involved in Pitx-mediated transactivation of the hPRL-164luc construct [13].
• Altogether, these results suggest that full responsiveness to several signaling pathways regulating the hPRL promoter requires the B2 Pitx binding site and that Pitx factors may be part of the proteic complex involved in these regulations [13].
• Computer analysis revealed the presence of Ptx1/Pitx1 signal sequences within the promoter region of human 11beta hydroxylase ( hCYP11B1) [14].
• In mice, Ptx1 and Ptx2 gene expression has been detected in the area of the pituitary primordium and is maintained throughout development in Rathke pouch and adult pituitary [15].

Anatomical context of PITX1

• Therefore, we analyzed the presence and role of Ptx1/Pitx1 in human adrenal cortex [14].
• Northern hybridization analysis of RNAs from human tissues revealed that human BFT is highly expressed in adult skeletal muscle and bladder [16].
• The Pitx homeobox gene family has important roles in vertebrate pituitary, eye, branchial arch, hindlimb and brain development, as well as a key function in regulating left-right asymmetry [17].
• Misexpression of Pitx1 in the forelimb results in the transformation and translocation of specific muscles, tendons, and bones of the forelimb so that they acquire a hindlimb-like morphology [18].
• Pitx1 determines the morphology of muscle, tendon, and bones of the hindlimb [18].

Associations of PITX1 with chemical compounds

• In addition, mutation in the B2 Pitx site results in attenuation of the promoter's responsiveness to forskolin, thyrotropin-releasing hormone, and epidermal growth factor [13].
• Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11beta-hydroxylase [14].
• We demonstrate here that Pitx-1 plays a crucial role in the regulation of the Chinook salmon luteinizing hormone beta gene promoter through a number of novel mechanisms [19].
• The time required for the association of BFT with HT29/C1 cells at 4 degrees C was inversely correlated with concentration [11].
• In addition, a selective COX-2 inhibitor, NS-398, significantly inhibited the increased cAMP level induced by BFT stimulation [20].
• Both PITX1 and PITX2C interacted with Smad3 (an effector of the activin signaling cascade in these cells) in coprecipitation experiments, and the PITX binding site mutation greatly inhibited Smad2/3/4-stimulated Fshb transcription [21].

Regulatory relationships of PITX1

• Interestingly, the NeuroD1 heterodimers activate transcription in synergy with Ptx1, a Bicoid-related homeodomain protein, which also contributes to corticotroph specificity of POMC transcription [22].
• However, despite multiple putative E-boxes in the MT(1) promoter, transfected Clock and Bmal1 were unable to regulate either basal or Pitx-1-stimulated MT(1) promoter activity [23].

Other interactions of PITX1

• Xpitx3 is the Xenopus homologue of the mouse Pitx3 gene and belongs to the family of RIEG/PITX homeobox genes [24].
• Taken together, these results suggested that the level of endogenous hPTX1 is not sufficient to block the function of NS5A for augmentation of virus-mediated IFN activity in HepG2 cells [4].
• BACKGROUND: Mutations of the prophet of PIT-1 (PROP-1), a paired-like homeodomain transcription factor which is responsible for early embryonic pituitary development, have recently been reported as a cause of combined pituitary hormone deficiency [25].
• Backfoot, a novel homeobox gene, maps to human chromosome 5 (BFT) and mouse chromosome 13 (Bft) [26].
• Subsequent analysis by fluorescent in situ hybridization places the human gene, PTX1, on 5q31, a region associated with Treacher Collins Franceschetti Syndrome [27].

Analytical, diagnostic and therapeutic context of PITX1

• By RT-PCR analysis, Ptx1 mRNA was expressed in all 18 cases of pituitary adenomas, including two cases negative for Ptx1 protein by immunohistochemistry [3].
• We investigated the localization of pituitary homeo box 1 (Ptx1) protein in five human non-neoplastic pituitaries and 73 of all types of pituitary adenomas using immunohistochemistry, and the expression of Ptx1 messenger RNA (mRNA) in 18 representative pituitary adenomas using the reverse transcriptase polymerase chain reaction (RT-PCR) technique [3].
• Mammalian two-hybrid assays revealed that Pitx-1 can homodimerize [19].
• IDN5109 given p.o. was highly active against the two human ovarian carcinoma xenografts 1A9 and HOC18 (90-100% tumor regressions) and showed significant activity on the paclitaxel-resistant MNB-PTX1 xenograft (10% tumor regressions) [28].
• Transmission and scanning electron microscopy after basolateral BFT confirmed a striking loss of cellular microvilli and complete dissolution of some tight junctions (zonula occludens) and zonula adherens without loss of desmosomes [29].

References