Precancerous carcinogenesis of human breast epithelial cells by chronic exposure to benzo[a]pyrene.
To understand carcinogenesis of human breast epithelial cells induced by chronic exposure to environmental pollutants, we studied biological and molecular changes in progression of cellular carcinogenesis induced by accumulated exposures to the potent environmental carcinogen benzo[a]pyrene (B[a]P). Increasing exposures of human breast epithelial MCF10A cells to B[a]P at picomolar concentrations resulted in cellular transformation from a noncancerous stage to precancerous substages, in which cells acquired the cancerous abilities of a reduced dependence on growth factors, anchorage-independent growth, and disruption in acini formation on reconstituted basement membranes. Using cDNA microarrays, we detected seven upregulated genes related to human cancers in B[a]P-transformed MCF10A cells. Using this model, we verified that green tea catechin significantly (P < 0.05) suppressed B[a]P-induced carcinogenesis. Our studies indicate that this cellular model may serve as a cost-efficient, in vitro system, mimicking the chronic carcinogenesis of breast cells that likely occurs in early stages of carcinogenesis in vivo, to identify agents that inhibit cellular carcinogenesis.
Siriwardhana
Nalin
N
Anticancer Molecular Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996, USA.
Wang
Hwa-Chain Robert
HC
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001940:Breast / Q000166:cytology*; D002392:Catechin / Q000627:therapeutic use; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000737:chemistry; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013662:Tea / Q000737:chemistry
D014408:Biomarkers, Tumor; D017931:DNA Primers; D012333:RNA, Messenger; D013662:Tea; D001564:Benzo(a)pyrene; D002392:Catechin