Current Colorectal Cancer Reports

, Volume 8, Issue 4, pp 277–289 | Cite as

Progastrin Peptides Increase the Risk of Developing Colonic Tumors: Impact on Colonic Stem Cells

  • Pomila SinghEmail author
  • Shubhashish Sarkar
  • Carla Kantara
  • Carrie Maxwell
Molecular Biology (S Anant, Section Editor)


Preneoplastic lesions (aberrant crypt foci, hyperplastic/dysplastic polyps) are believed to be precursors of sporadic colorectal tumors (adenomas, adenocarcinomas). Aberrant crypt foci and hyperplastic/dysplastic polyps likely originate from abnormal growth of colonic crypts in response to aberrant queues in the microenvironment of colonic crypts. Thus, identifying factors which regulate homeostatic versus aberrant proliferation/apoptosis of colonocytes, especially stem/progenitor cells, may lead to effective preventative/treatment strategies. On the basis of this philosophy, the role of growth factors/peptide hormones potentially available in the circulation/microenvironment of colonic crypts is being examined extensively. Since the time gastrins were discovered as trophic (growth) factors for gastrointestinal cells, the effect of gastrins on the growth of normal/cancer cells has been investigated, leading to many discoveries. Seminal discoveries in the area of gastrins and colon cancer as it relates to molecular pathways associated with formation of colonic tumors are reviewed and the possible impact on diagnostic/preventative/treatment strategies is discussed.


Aberrant crypt foci Adenomas adenocarcinomas Akt Cell-surface-associated annexin A2 Cancer-stem cells β-Catenin Cluster of differentiation 44 Cluster of differentiation 133, CpG island methylator phenotype Chromosomal instability Colonic crypts Colorectal cancer Colon carcinogenesis Curcumin Cytochrome c oxidase subunit Vb Doublecortin–Ca+2/calmodulin kinase like protein Extracellular-signal-regulated kinases Hyperplastic polyps Janus kinase Leucine-rich-repeat-containing G-protein-coupled-receptor 5 Microsatellite-instability Nuclear factor κB p38 mitogen-activated protein kinase Progastrin/glycine-extended gastrin Phosphoinositide 3-kinase Rous Sarcoma viral gene encoded kinase Signal transducer and activator of transcription 3 



Annexin A2






Cholecystokinin type 2 receptor


Clathrin-mediated endocytosis


Cytochrome c oxidase subunit Vb


Colorectal cancer


Cell-surface-associated annexin A2


Doublecortin–Ca+2/calmodulin kinase like protein 1


Epidermal growth factor


Epidermal growth factor receptor


Extracellular-signal-regulated kinase

Fabp-PG mice

Mice overexpressing human progastrin in the intestines in response to fatty acid binding proteins


Glycine-extended gastrin

hGAS mice

Mice constitutively overexpressing human progastrin


Insulin-like growth factor

INS-GAS mice

Mice overexpressing amidated gastrins in response to insulin


Leucine-rich-repeat-containing G-protein-coupled receptor 5


Mitogen-activated protein kinase


Matrix metalloproteinase


Nuclear factor κB




Signal transducer and activator of transcription 3



P. Singh is supported by NIH grant RO1-CA97959-(9). The authors thank Cheryl Simmons for her valuable secretarial help in preparing the manuscript and Claiborne Fant for helping with the graphic design of the figure.


P. Singh: patent regarding vaccine against prograstrin pending (technology associated with the vaccine has been licensed by BioRéalités SAS, with licensing fees received by University of Texas Medical Branch); S. Sarkar: none; C. Kantara: none; C. Maxwell: none.


Published papers of particular interest, published recently, have been highlighted as: • Of importance

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Pomila Singh
    • 1
    Email author
  • Shubhashish Sarkar
    • 1
  • Carla Kantara
    • 1
  • Carrie Maxwell
    • 1
  1. 1.Department of Neuroscience and Cell BiologyUniversity of Texas Medical BranchGalvestonUSA

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