Journal Article

Stage matters: choosing relevant model systems to address hypotheses in diet and cancer chemoprevention research

Jenifer I. Fenton and Norman G. Hord

in Carcinogenesis

Volume 27, issue 5, pages 893-902
Published in print May 2006 | ISSN: 0143-3334
Published online February 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi355
Stage matters: choosing relevant model systems to address hypotheses in diet and cancer chemoprevention research

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Clinical evidence reveals that the efficacy of dietary factors to prevent cancer is probably stage-dependent. The ability to demonstrate stage-specific effects of dietary compounds on normal, preneoplastic and malignant cell models may provide insights into puzzling clinical results from cancer chemoprevention trials. The relevance of these models to the field of cancer prevention is immense and will undoubtedly facilitate the ability to discover which dietary factors are most effective at preventing cancer and which, if any, specific steps in neoplastic transformation render cells refractory to the effects of dietary compounds. There are illustrative examples where exposure of high-risk individuals to dietary chemopreventive agents increases rather than decreases cancer risk. While geneticists and clinical oncologists acknowledge the morphological continuum along which tumors develop in specific tissues, tumor cells, rather than normal and preneoplastic cells, continue to be the primary in vitro reductionist tool employed to elucidate mechanisms underlying disease progression and to investigate the potential utility of dietary as well as other chemopreventive agents. Currently, there are few relevant model systems to study the progression of neoplastic transformation, especially in epithelial cells. We highlight examples of model systems isolated from prostate, breast, endometrial and intestinal tissue, with special emphasis on a specific set of non-tumorigenic, conditionally immortal cell lines derived from C57/BL6 mice [YAMC (Young Adult Mouse Colon cells; Apc+/+) cells and IMCE (Immorto-Min Colonic Epithelium cells; ApcMin/+) cells] that have yielded important information on early events in colorectal neoplasia development. These cell lines are an illustrative example of how researchers can examine stage-dependent effects of specific dietary components on carcinogenesis. The utilization of cell culture systems modeling early, middle and late stages of tumorigenesis will yield important insights into mechanisms by which dietary components impact cancer progression.

Keywords: APC, adenomatous polyposis coli; ATRA, all-trans-retinoic acid; Caco-2, Caucasian colon adenocarcinoma-2; CEC, colon epithelial cell; CRC, colorectal cancer; ECM, extracellular matrix; FAP, familial adenomatous polyposis; IMCE, Immorto-min colonic epithelium; YAMC, young adult mouse colon

Journal Article.  9197 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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