title: A metabolic hypothesis of cell growth and death in pancreatic cancer.
abstract: BACKGROUND
  Tumor cells, just as other living cells, possess the potential for proliferation, differentiation, cell cycle arrest, and apoptosis. There is a specific metabolic phenotype associated with each of these conditions, characterized by the production of both energy and special substrates necessary for the cells to function in that particular state. Unlike that of normal living cells, the metabolic phenotype of tumor cells supports the proliferative state.
  
  
  OBJECTIVE
  To present the metabolic hypothesis that (1) cell transformation and tumor growth are associated with the activation of metabolic enzymes that increase glucose carbon utilization for nucleic acid synthesis, while enzymes of the lipid and amino acid synthesis pathways are activated in tumor growth inhibition, and (2) phosphorylation and allosteric and transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate and sustain cell transformation from one condition to another.
  
  
  CONCLUSIONS
  Evidence is presented that demonstrates opposite changes in metabolic phenotypes induced by TGF-beta, a cell-transforming agent, and tumor growth-inhibiting phytochemicals such as genistein and Avemar, or novel synthetic anti-leukemic drugs such as STI571 (Gleevec). Intermediary metabolic enzymes that mediate the growth signaling pathways and promote malignant cell transformation may serve as high-efficacy nongenetic novel targets for cancer therapies.
authors.affiliation: Harbor-University of California Los Angeles Research and Education Institute, UCLA School of Medicine, Torrance, California 90502, USA. boros@gcrc.rei.edu
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Boros
authors.forename: Wai-Nang Paul
authors.initials: WN
authors.lastname: Lee
authors.forename: Vay Liang W
authors.initials: VL
authors.lastname: Go
mesh_terms: D017209:Apoptosis; D002250:Carbon Radioisotopes; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation; D002455:Cell Division; D002952:Citric Acid Cycle; D003903:Deuterium; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007554:Isotopes; D013058:Mass Spectrometry; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D007554:Isotopes; D016212:Transforming Growth Factor beta; D003903:Deuterium; D019833:Genistein; D005947:Glucose