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Gene Review

REG4  -  regenerating islet-derived family, member 4

Homo sapiens

Synonyms: GISP, Gastrointestinal secretory protein, REG-4, REG-IV, REG-like protein, ...
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Disease relevance of REG4


High impact information on REG4


Biological context of REG4


Anatomical context of REG4


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


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].


  1. Novel tumor marker REG4 detected in serum of patients with resectable pancreatic cancer and feasibility for antibody therapy targeting REG4. Takehara, A., Eguchi, H., Ohigashi, H., Ishikawa, O., Kasugai, T., Hosokawa, M., Katagiri, T., Nakamura, Y., Nakagawa, H. Cancer Sci. (2006) [Pubmed]
  2. Reg IV activates the epidermal growth factor receptor/Akt/AP-1 signaling pathway in colon adenocarcinomas. Bishnupuri, K.S., Luo, Q., Murmu, N., Houchen, C.W., Anant, S., Dieckgraefe, B.K. Gastroenterology (2006) [Pubmed]
  3. Reg IV: a promising marker of hormone refractory metastatic prostate cancer. Gu, Z., Rubin, M.A., Yang, Y., Deprimo, S.E., Zhao, H., Horvath, S., Brooks, J.D., Loda, M., Reiter, R.E. Clin. Cancer Res. (2005) [Pubmed]
  4. Overexpression of Reg IV in colorectal adenoma. Zhang, Y., Lai, M., Lv, B., Gu, X., Wang, H., Zhu, Y., Zhu, Y., Shao, L., Wang, G. Cancer Lett. (2003) [Pubmed]
  5. RELP, a novel human REG-like protein with up-regulated expression in inflammatory and metaplastic gastrointestinal mucosa. Kämäräinen, M., Heiskala, K., Knuutila, S., Heiskala, M., Winqvist, O., Andersson, L.C. Am. J. Pathol. (2003) [Pubmed]
  6. Expression and localization of Reg IV in human neoplastic and non-neoplastic tissues: Reg IV expression is associated with intestinal and neuroendocrine differentiation in gastric adenocarcinoma. Oue, N., Mitani, Y., Aung, P.P., Sakakura, C., Takeshima, Y., Kaneko, M., Noguchi, T., Nakayama, H., Yasui, W. J. Pathol. (2005) [Pubmed]
  7. Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas. Violette, S., Festor, E., Pandrea-Vasile, I., Mitchell, V., Adida, C., Dussaulx, E., Lacorte, J.M., Chambaz, J., Lacasa, M., Lesuffleur, T. Int. J. Cancer (2003) [Pubmed]
  8. Phylogenetic and physiological diversity of microorganisms isolated from a deep greenland glacier ice core. Miteva, V.I., Sheridan, P.P., Brenchley, J.E. Appl. Environ. Microbiol. (2004) [Pubmed]
  9. Molecular cloning, expression and chromosomal localization of a novel human REG family gene, REG III. Nata, K., Liu, Y., Xu, L., Ikeda, T., Akiyama, T., Noguchi, N., Kawaguchi, S., Yamauchi, A., Takahashi, I., Shervani, N.J., Onogawa, T., Takasawa, S., Okamoto, H. Gene (2004) [Pubmed]
  10. Cytochrome P450 (CYP)9A1 in Heliothis virescens: the first member of a new CYP family. Rose, R.L., Goh, D., Thompson, D.M., Verma, K.D., Heckel, D.G., Gahan, L.J., Roe, R.M., Hodgson, E. Insect Biochem. Mol. Biol. (1997) [Pubmed]
  11. Comparison of TRH and anorexigenic peptide on food intake and gastrointestinal secretions. Konturek, S.J., Tasler, J., Jaworek, J., Dobrzańska, M., Coy, D.H., Schally, A.V. Peptides (1981) [Pubmed]
  12. Impaired release of peptide YY in patients with proctocolectomy and ileal pouch-anal anastomosis. van Battum, P.L., Hopman, W.P., Salemans, J.M., Kuijpers, J.H., Nagengast, F.M., Jansen, J.B. Scand. J. Gastroenterol. (1999) [Pubmed]
  13. Expression of a novel regenerating gene product, Reg IV, by high density fermentation in Pichia pastoris: production, purification, and characterization. Li, A., Crimmins, D.L., Luo, Q., Hartupee, J., Landt, Y., Ladenson, J.H., Wilson, D., Anant, S., Dieckgraefe, B.K. Protein Expr. Purif. (2003) [Pubmed]
  14. Gene expression patterns distinguish colonoscopically isolated human aberrant crypt foci from normal colonic mucosa. Glebov, O.K., Rodriguez, L.M., Soballe, P., Denobile, J., Cliatt, J., Nakahara, K., Kirsch, I.R. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
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