Disease relevance of IFT88

• Characterization of the human homologue of the mouse Tg737 candidate polycystic kidney disease gene [1].
• Structure and expression of Tg737, a putative tumor suppressor gene, in human hepatocellular carcinomas [2].
• Sequence analysis of the human hTg737 gene and its polymorphic sites in patients with autosomal recessive polycystic kidney disease [3].
• The 4 deep periodontal pockets in each patient were assigned to be irrigated with 150 ml CHX (0.12%), TTC (10 or 50 mg/ml; TTC10, TTC50), or sterile saline (control) in a single episode [4].

High impact information on IFT88

• Chromosome mapping experiments revealed that the hTg737 gene maps near the centromere on the long arm of human chromosome 13, at position 13q12 [1].
• The human gene, called hTg737, is expressed with a broad tissue distribution that includes the the kidney and liver, and gives rise to a 2.9 kb mRNA [1].
• Thus, to investigate the role of cilia during limb development, we generated a conditional allele of the IFT protein Ift88 (polaris) [5].
• Deletions of the Tg737 gene, whose product is involved in liver oval cell proliferation, differentiation, and ploidy control, have been recently shown in chemically induced rat liver tumors and in a limited series of patients with hepatocellular carcinoma (HCC) [2].
• Ectopic re-expression of the Tg737 gene in a Tg737 deleted mouse liver tumor cell line resulted in suppression of tumorigenic growth, without altering in vitro cell culture growth [6].

Biological context of IFT88

• Thus, Tg737 has been proposed as a candidate new liver-specific tumor suppressor gene [2].
• Ectopic expression of the Tg737 gene results in multinucleated cells, loss of Tg737 gene expression results in the proliferation of liver stem cells (oval cells) without concomitant differentiation, and reexpression of the Tg737 gene reestablished responsiveness to external differentiation factors [6].
• DNA sequence analysis of the human Tg737 gene was performed in 36 patients with the autosomal recessive form of polycystic kidney disease (ARPKD) [3].

Anatomical context of IFT88

• The Tg737 gene was found to be altered in approximately 40% of the rodent chemically-induced liver tumors, 40% of the human liver tumors, and in liver, kidney and pancreatic human tumor cell lines [6].
• The Tg737 gene was investigated for gross alterations in a series of rodent/human liver tumors and human tumorigenic cell lines [6].
• Here we provide insights into the mechanism by which defects in an IFT protein, Tg737/Polaris, affect Shh signaling in the murine limb bud [7].

Associations of IFT88 with chemical compounds

• Treatment of mice which are either homozygous normal or heterozygous deleted at the Tg737 locus with the carcinogen diethylnitrosamine resulted in an increase in preneoplastic foci formation in the Tg737 heterozygous deleted mice [6].
• To further assess the biological function of Tg737 and its role in the mutant pathology, we identified the cell population expressing Tg737 and determined the subcellular localization of its protein product called Polaris [8].

Other interactions of IFT88

• The tetratricopeptide repeat containing Tg737 gene is a liver neoplasia tumor suppressor gene [6].

Analytical, diagnostic and therapeutic context of IFT88

• We failed to identify deletions or gross alterations of the Tg737 gene by both PCR and Southern blot analyses [2].
• Northern blots showed comparable accumulation of normal Tg737 transcripts in both tumorous and nontumorous tissues [2].

References