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Gene Review

PGC  -  progastricsin (pepsinogen C)

Homo sapiens

Synonyms: Gastricsin, PEPC, PGII, Pepsinogen C
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Disease relevance of PGC


Psychiatry related information on PGC

  • As expected, men who reported overall change in frequency of social interaction scored substantially lower on the PGC Morale Scale than those who perceived no change [5].
  • Data on 150 people, between the ages of 50 and 82, yielded high correlations between three measures of well-being (the MUNSH, the LSI-Z, and the PGC) and the Edwards Social Desirability Scale, but only moderate ones between well-being scales and the Marlowe-Crowne Social Desirability Scale [6].

High impact information on PGC

  • The maintenance of germline-like methylation with a switch in PGC fate is somewhat analogous to the situation in lag mutants from Volvox, which retain large gonidial-sized cells that can nevertheless initiate somatic differentiation [7].
  • Basal serum gastrin, serum pepsinogen A, and serum pepsinogen C concentrations were monitored at regular intervals [8].
  • Human gastric mucosa contains three immunochemically distinguishable aspartic proteinases, pepsinogen I (pepsinogen A), pepsinogen II (pepsinogen C, progastricsin), and a nonpepsinogen proteinase also termed slow moving proteinase (SMP) [9].
  • Based on their origin and demonstrated properties, these human PGC-derived cultures meet the criteria for pluripotent stem cells and most closely resemble EG cells [10].
  • PURPOSE: Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas [11].

Chemical compound and disease context of PGC

  • Studies using nifedipine with both the unilaterally nephrectomized DOCA salt rat model and the 1 5/6 nephrectomy model demonstrated reduced proteinuria and glomerulosclerosis that was independent of reduced PGC [12].
  • Patients cured of H. pylori infection showed a significant decrease in the histological activity of both antral and body gastritis (P< 0.0001), a significant drop in immunoglobulin (Ig) G anti-H. pylori antibodies (P< 0.0001) and pepsinogen (PG) C (P<0.0001) and an increase in the PGA/PGC ratio (P<0.0001) [13].
  • CONCLUSIONS: The 7 day, lansoprazole-based triple therapy was well tolerated and highly effective in the cure of H. pylori infection, the reduction of symptoms, chronic gastritis activity and serum levels of IgG anti-H. pylori antibodies and PGC [13].
  • Hormonal regulation of the human pepsinogen C gene in breast cancer cells. Identification of a cis-acting element mediating its induction by androgens, glucocorticoids, and progesterone [14].
  • Reverse transcription-polymerase chain reaction analysis in a series of breast cancer cell lines confirmed the amplification of pepsinogen C mRNA after induction with dihydrotestosterone, in those cells expressing the androgen receptor mRNA [14].

Biological context of PGC


Anatomical context of PGC


Associations of PGC with chemical compounds

  • Urea-containing polyacrylamide gel electrophoresis of the eluted material consistently revealed two main signals of 35S radioactivity (one with an M(r) between 600,000 and 750,000 [PGA] and the other with an M(r) between 120,000 and 180,000 [PGC]) [21].
  • Several different collection strategies were tested, using a selection of liquids (methanol, toluene, methyl tert-butyl ether, acetonitrile), inert and solid-phase extraction materials (Nexus, Oasis, LiChrolut), and 1-cm liquid chromatography precolumns (porous graphitic carbon, PGC) [22].
  • 3. In contrast, PRA was lower in the PGC diabetic patients (1.3 +/- 0.3 pmol of angiotensin 1 h-1 ml-1) compared with the other groups (2.5 +/- 0.5 and 2.1 +/- 0.2 pmol of angiotensin I h-1 ml-1, P less than 0.05) [23].
  • The most striking result was a significantly higher promoter methylation frequency of O6-methylguanine methyl transferase (MGMT) in BC compared with JC and PGC (0.7 vs. 0.08 vs. 0.29, respectively; p = 0.011; methylation exclusively in tumors), confirmed immunohistochemically by a significant loss of MGMT protein in BC (p = 0.006) [24].
  • Eight serum and urine samples were obtained after raising the serum PGA and PGC levels by oral administration of omeprazole [25].

Regulatory relationships of PGC

  • The proteolytic activity of PA-PGC was used for digesting the blocking reagent around the target antigen (in situ digestion method) or casein-clotting in the agarose plate containing skimmed milk (caseogram print method) [26].

Other interactions of PGC

  • The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays [27].
  • The human digestive enzyme gastricsin (pepsin C) is an aspartic proteinase that is synthesized as the inactive precursor (zymogen) progastricsin (pepsinogen C or hPGC) [28].
  • Following resolution by PGC chromatography, MALDI-MS in conjunction with alkaline phosphatase treatment identified Ser(555), Ser(556), Ser(724), and Ser(727) as sites of phosphorylation on MLK3 [29].
  • The well-orchestrated expression of the multitude of proteins involved in these adaptations is mediated by the rapid activation of PPAR gamma co-activator (PGC) 1, a protein that binds to various transcription factors to maximize transcriptional activity [30].
  • Frequencies of p16INK4a promoter methylation were 0.5 (BC), 0.42 (JC) and 0.29 (PGC; n.s.), but methylation was almost absent in NT controls [24].

Analytical, diagnostic and therapeutic context of PGC


  1. Helicobacter pylori genotypes influence serum pepsinogen C levels. Plebani, M., Basso, D., Navaglia, F., DiMario, F. Helicobacter (1997) [Pubmed]
  2. Association between pepsinogen C gene polymorphism and genetic predisposition to gastric cancer. Liu, H.J., Guo, X.L., Dong, M., Wang, L., Yuan, Y. World J. Gastroenterol. (2003) [Pubmed]
  3. Gastric proteases in Barrett's esophagus. Westerveld, B.D., Pals, G., Bosma, A., Defize, J., Pronk, J.C., Frants, R.R., Eriksson, A.W., Meuwissen, S.G. Gastroenterology (1987) [Pubmed]
  4. Isolation and characterization of a pepsin C zymogen produced by human breast tissues. Sánchez, L.M., Freije, J.P., Merino, A.M., Vizoso, F., Foltmann, B., López-Otín, C. J. Biol. Chem. (1992) [Pubmed]
  5. Friendship, social interaction and subjective well-being of older men in an institutional setting. Tesch, S., Whitbourne, S.K., Nehrke, M.F. International journal of aging & human development. (1981) [Pubmed]
  6. Social desirability in measures of subjective well-being: a systematic evaluation. Kozma, A., Stones, M.J. Journal of gerontology. (1987) [Pubmed]
  7. The germline: familiar and newly uncovered properties. Wei, G., Mahowald, A.P. Annu. Rev. Genet. (1994) [Pubmed]
  8. Effect of long-term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis. Jansen, J.B., Klinkenberg-Knol, E.C., Meuwissen, S.G., De Bruijne, J.W., Festen, H.P., Snel, P., Lückers, A.E., Biemond, I., Lamers, C.B. Gastroenterology (1990) [Pubmed]
  9. Slow moving proteinase. Isolation, characterization, and immunohistochemical localization in gastric mucosa. Samloff, I.M., Taggart, R.T., Shiraishi, T., Branch, T., Reid, W.A., Heath, R., Lewis, R.W., Valler, M.J., Kay, J. Gastroenterology (1987) [Pubmed]
  10. Derivation of pluripotent stem cells from cultured human primordial germ cells. Shamblott, M.J., Axelman, J., Wang, S., Bugg, E.M., Littlefield, J.W., Donovan, P.J., Blumenthal, P.D., Huggins, G.R., Gearhart, J.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. Pepsinogen C is a new prognostic marker in primary breast cancer. Vizoso, F., Sánchez, L.M., Díez-Itza, I., Merino, A.M., López-Otín, C. J. Clin. Oncol. (1995) [Pubmed]
  12. Renal effects of calcium antagonists in diabetes mellitus. An overview of studies in animal models and in humans. Bakris, G.L. Am. J. Hypertens. (1991) [Pubmed]
  13. Efficacy of 7 day lansoprazole-based triple therapy for Helicobacter pylori infection in elderly patients. Pilotto, A., Franceschi, M., Leandro, G., Bozzola, L., Fortunato, A., Rassu, M., Meli, S., Soffiati, G., Scagnelli, M., Di Mario, F., Valerio, G. J. Gastroenterol. Hepatol. (1999) [Pubmed]
  14. Hormonal regulation of the human pepsinogen C gene in breast cancer cells. Identification of a cis-acting element mediating its induction by androgens, glucocorticoids, and progesterone. Balbín, M., López-Otín, C. J. Biol. Chem. (1996) [Pubmed]
  15. Tubular reabsorption of pepsinogen isozymogens in man studied by the inhibition of tubular protein reabsorption with dibasic amino acids. ten Dam, M.A., Zwiers, A., Crusius, J.B., Pals, G., Van Kamp, G.J., Meuwissen, S.G., Donker, A.J., ten Kate, R.W. Clin. Sci. (1991) [Pubmed]
  16. Human pepsinogen C (progastricsin). Isolation of cDNA clones, localization to chromosome 6, and sequence homology with pepsinogen A. Taggart, R.T., Cass, L.G., Mohandas, T.K., Derby, P., Barr, P.J., Pals, G., Bell, G.I. J. Biol. Chem. (1989) [Pubmed]
  17. Human pepsinogen C (progastricsin) polymorphism: evidence for a single locus located at 6p21.1-pter. Pals, G., Azuma, T., Mohandas, T.K., Bell, G.I., Bacon, J., Samloff, I.M., Walz, D.A., Barr, P.J., Taggart, R.T. Genomics (1989) [Pubmed]
  18. Immunofluorometric assay of pepsinogen C and preliminary clinical applications. Diamandis, E.P., Nadkarni, S., Bhaumik, B., Abdelrahman, A., Melegos, D.N., Borchert, G., Black, M.H., Alonso, M., Salas, A., de los Toyos, J.R., Sampedro, A., López-Otín, C. Clin. Chem. (1997) [Pubmed]
  19. Methylation and expression of human pepsinogen genes in normal tissues and their alteration in stomach cancer. Ichinose, M., Miki, K., Wong, R.N., Tatematsu, M., Furihata, C., Konishi, T., Matsushima, M., Tanji, M., Sano, J., Kurokawa, K. Jpn. J. Cancer Res. (1991) [Pubmed]
  20. Prognostic factors in gastric stump carcinoma. Thorban, S., Böttcher, K., Etter, M., Roder, J.D., Busch, R., Siewert, J.R. Ann. Surg. (2000) [Pubmed]
  21. Isolation and characterization of tissue-type plasminogen activator- binding proteoglycans from human umbilical vein endothelial cells. Böhm, T., Geiger, M., Binder, B.R. Arterioscler. Thromb. Vasc. Biol. (1996) [Pubmed]
  22. Supercritical fluid extraction of energetic nitroaromatic compounds and their degradation products in soil samples. Batlle, R., Nerín, C., Crescenzi, C., Carlsson, H. Anal. Chem. (2005) [Pubmed]
  23. Increased plasma atrial natriuretic factor and reduced plasma renin in patients with poorly controlled diabetes mellitus. Bell, G.M., Bernstein, R.K., Laragh, J.H., Atlas, S.A., James, G.D., Pecker, M.S., Sealey, J.E. Clin. Sci. (1989) [Pubmed]
  24. Promoter hypermethylation of p16INK4a, E-cadherin, O6-MGMT, DAPK and FHIT in adenocarcinomas of the esophagus, esophagogastric junction and proximal stomach. Schildhaus, H.U., Kröckel, I., Lippert, H., Malfertheiner, P., Roessner, A., Schneider-Stock, R. Int. J. Oncol. (2005) [Pubmed]
  25. Tubular handling of pepsinogen A and C in man: evidence for two distinct tubular reabsorption mechanisms for low molecular weight proteins in man. ten Kate, R.W., Pals, G., Donker, A.J., Pronk, J.C., Meuwissen, S.G. Nephron (1989) [Pubmed]
  26. Detection of blotted antigen using a fusion protein between protein A and pepsinogen C. Aoki, T., Satoh, M., Watabe, H. J. Biochem. (1998) [Pubmed]
  27. Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics. Broutet, N., Plebani, M., Sakarovitch, C., Sipponen, P., Mégraud, F. Br. J. Cancer (2003) [Pubmed]
  28. Structural characterization of activation 'intermediate 2' on the pathway to human gastricsin. Khan, A.R., Cherney, M.M., Tarasova, N.I., James, M.N. Nat. Struct. Biol. (1997) [Pubmed]
  29. Identification of in vivo phosphorylation sites of MLK3 by mass spectrometry and phosphopeptide mapping. Vacratsis, P.O., Phinney, B.S., Gage, D.A., Gallo, K.A. Biochemistry (2002) [Pubmed]
  30. Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle. Ojuka, E.O. The Proceedings of the Nutrition Society. (2004) [Pubmed]
  31. Expression and clinical significance of pepsinogen C in uveal melanomas. Alvarez, M.L., González, L.O., Barbón, J.J., Astudillo, A., Vizoso, F.J. Int. J. Biol. Markers (2004) [Pubmed]
  32. Pepsinogen A and C serum levels in relation to acute NSAID-associated mucosal lesions in healthy volunteers. Aabakken, L., Axelsson, C.K., Szecsi, P.B. Scand. J. Gastroenterol. (1993) [Pubmed]
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