Disease relevance of REG4

• Novel tumor marker REG4 detected in serum of patients with resectable pancreatic cancer and feasibility for antibody therapy targeting REG4 [1].
• Reg IV activates the epidermal growth factor receptor/Akt/AP-1 signaling pathway in colon adenocarcinomas [2].
• BACKGROUND & AIMS: Reg IV, a secreted protein and member of the Reg multigene family, is up-regulated in malignancies of the human gastrointestinal tract, including colorectal carcinoma (CRC) [2].
• Reg IV: a promising marker of hormone refractory metastatic prostate cancer [3].
• Overexpression of Reg IV in colorectal adenoma [4].

High impact information on REG4

• However, in vitro signal transduction pathway(s) utilized by Reg IV are not yet known [2].
• RELP, a novel human REG-like protein with up-regulated expression in inflammatory and metaplastic gastrointestinal mucosa [5].
• Neuroendocrine cells of the small intestine and colon showed strong expression of Reg IV, whereas goblet cells of the small intestine and colon showed weak or no expression of Reg IV [6].
• Expression of Reg IV was detected in 14 (93.3%) of 15 colorectal carcinoid tumours [6].
• Among 143 gastric adenocarcinomas, Reg IV expression was detected in 42 (29.4%) and was associated with both the intestinal mucin phenotype and neuroendocrine differentiation [6].

Biological context of REG4

• Furthermore, we found that knockdown of endogenous REG4 expression in PDAC cell lines with small interfering RNA caused a decrease in cell viability [1].
• Reg IV mRNA-positive tumor cells display different phenotypes: mucus-secreting, enterocyte-like or undifferentiated [7].
• We studied a sample from the GISP 2 (Greenland Ice Sheet Project) ice core to determine the diversity and survival of microorganisms trapped in the ice at least 120,000 years ago [8].
• By database searching and PCR analysis using a yeast artificial chromosome clone, the human REG family genes on chromosome 2, except for REG IV on chromosome 1, were mapped to a contiguous 140 kb region of the human chromosome 2p12 [9].
• The pattern of restriction fragment length polymorphism (RELP) variation in offspring of single-pair matings demonstrated autosomal inheritance of CYP9A1 and enabled its assignment to linkage group 7 [10].

Anatomical context of REG4

• Concordantly, addition of recombinant REG4 to the culture medium enhanced growth of a PDAC cell line in a dose-dependent manner [1].
• In normal tissue, Reg IV mRNA-positive cells are mostly enteroendocrine cells and goblet cells [7].
• Interestingly, whereas Reg IV expression is low in normal colon, its level in normal small intestine is similar to that in some colorectal tumors [7].
• Insulin-producing beta cells of the endocrine pancreas were positive for Reg IV [6].
• Reg IV expression was also detected in 5 (21.7%) of 23 ductal adenocarcinomas of the pancreas [6].

Associations of REG4 with chemical compounds

• The results indicate that TRH and AP have similar inhibitory action on feeding and gastrointestinal secretory activity and that they may be involved in peptidergic mediation of satiety and gastrointestinal secretion [11].

Regulatory relationships of REG4

• PYY inhibits upper gastrointestinal secretory and motor functions [12].
• Recombinant human Reg IV was efficiently expressed under the control of the AOX1 gene promoter in Pichia pastoris using the MutS strain KM71H [13].

Other interactions of REG4

• CONCLUSIONS: Reg IV is a potent activator of the EGF receptor/Akt/AP-1 signaling pathway in CRC [2].
• Furthermore, ACF and NM samples, including six pairs of ACF and NM samples that had not previously been analyzed by array hybridization, can be correctly classified on the basis of the overexpression in ACF of three selected genes (REG4, SRPN-B5, and TRIM29) evaluated by real-time reverse transcription-PCR [14].

Analytical, diagnostic and therapeutic context of REG4

• We also detected significant elevation of REG4 in the serum of some patients with early-stage PDAC using our enzyme-linked immunosorbent assay system, indicating the possibility of REG4 as a new serological marker of PDAC [1].
• We here report overexpression of REG4, a new member of the regenerating islet-derived (REG) family, in PDAC cells on the basis of genome-wide cDNA microarray analysis as well as reverse transcription-polymerase chain reaction and immunohistochemical analysis [1].
• This gene, Reg IV, was confirmed to be differentially expressed in the LAPC-9 hormone refractory xenograft [3].
• Northern blot and real-time PCR analysis showed that Reg IV is more strongly expressed in 71% of colorectal tumors (in particular in mucinous carcinomas) than in normal colon tissues [7].
• Detection of Reg IV overexpression may be useful in the early diagnosis of carcinomatous transformation of adenoma [4].

References