2004) (4) NESP55, with a length of 245 amino acids, is maternally expressed and encoded by NESP55 exon. But there is no evidence showing that seven-transmembrane receptors activating Gsα can also activate XLαs (3) protein ALEX, with a length of 626 amino acid residues, is the product of paternal expression of XL exon and possibly contributes to the inhibition of AC activity in XLαs subunit (Abramowitz et al. XLαs is one of the isoforms of Gsα, with similar downstream receptor to Gsα. The result showed four kinds of proteins encoded by GNAS: (1) Gsα, with a length of 394 amino acid residues, is encoded by GNAS exon 1–13 (2) XLαs, with a length of 1037 amino acid residues, is paternally expressed and responsible for the stimulation of AC-cAMP–PKA signaling pathway. The UniProt database ( ) was used to search for proteins encoded by GNAS, with the searching term as “gene: GNAS AND reviewed: yes AND organism: “Homo sapiens (Human) ””. NESP55 is maternally expressed, while NESP anti sense, XLαs, and exon 1A are paternally expressed (Fig. The imprinted expression patterns of the aforementioned promoters are highly complicated. The resulted exon 1A transcripts were presumed to be untranslated mRNAs. The coding sequence is within the upstream of Gsα exon 1, leaving exon 2–13 untranslated region (2) promoter 2, about 2–3 kb upstream of XL exon, initiates NESP55 exon transcription from the opposite direction (3) promoter 3, about 35 kb upstream of Gsα exon 1, encodes extra-large alphas protein (XLαs), whose coding sequence is composed of XL exon and Gsα exon 1 (4) promoter 4 locates at about 2.5 kb upstream of Gsα exon 1. 2001): (1) promoter 1, about 49 kb upstream of Gsα exon 1, encodes neuroendocrine secretory protein 55 (NESP55). There are four kinds of alternative promoter regions upstream of Gsα exon 1 (Weinstein et al. ( 2005) that Gsα imprinted with tissue-specific pattern in kidney cortex, thyroid gland, pituitary gland, and ovary, which is mainly maternally expressed. The promoter region of Gsα is located at the CpG island upstream of exon 1, which is usually unmethylated in alleles of both parental origins (Bird 1986 Gardiner-Garden and Frommer 1987). To have a better insight into the role of GNAS gene in PMP, we systemically reviewed the biological background of GNAS, current studies concerning the variant feature of GNAS, the impacts of GNAS mutations on mucin expression, tumor cell proliferation, and clinical–pathological characteristics and prognosis. It has been reported that Kirsten rat sarcoma viral oncogene homolog ( KRAS) and guanine nucleotide-binding protein alpha subunit ( GNAS) are two of the most frequently detected variants in PMP, and GNAS mutation plays an important role in the regulation of mucin expression (Bradbury 2000 Jarry et al. One of the difficulties in studying PMP is the scarcity of knowledge in the fundamental molecular mechanisms underlying mucus hypersecretion. 2014, 2019).Īlthough treated with CRS plus HIPEC, patients frequently suffered from relapse, presenting aggravated “jelly belly”. 2018), and has been recommended by Peritoneal Surface Oncology Group International (PSOGI) as the standard treatment of PMP (Li et al. Aggressive cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) could bring significant survival benefit to PMP (Chua et al. 2002a, b), which gradually leads to intraperitoneal organ adhesion, bowel obstruction, malnutrition, and eventually cachexia and death. The chronic and uncontrollable mucus accumulation is one of the major clinical features of PMP (O’Connell et al. PMP is characterized by a large volume of mucinous ascites, multiple peritoneal implantations, omental cake, and ovarian involvement in women macroscopically, and abundant mucus pools microscopically. Pseudomyxoma peritonei (PMP) is a rare clinical malignancy syndrome usually caused by the perforation of appendiceal mucinous tumor and the “redistribution phenomenon” of mucus and tumor cells, with an incidence of 1–2/million (Mittal et al.
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