Models of progression spanning preneoplasia and metastasis: the human MCF10AneoT.TGn series and a panel of mouse mammary tumor subpopulations.
The two models described offer an opportunity to determine relevant genetic alterations during progression from preneoplasia to metastatic disease while avoiding genetic noise among individuals (patients and mice) and independent cancers. The human preneoplastic MCF10AneoT.TGn model allows the identification of altered genes as progression occurs sporadically and affords a method of directly testing the gene affect by introduction into non-expressing variants. The model also will allow testing suspected oncogenes and suppressor genes identified in other cancers. However, its value in the latter studies may be limited because genes may not alter MCF10AneoT phenotypes due to other unidentifiable differences between the MCF10 model and the cancer in which the gene was identified. The mouse model allows similar cause and effect studies to determine at which specific steps metastasis genes might be important. The model also provides an opportunity to determine which host response elements are important deterrents at each step in metastasis and in different organ sites. Together, these models have the potential to elucidate a genetic sequence of progression in breast comparable with that being constructed for colon carcinoma [16].
Miller
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Breast Cancer Program, Michigan Cancer Foundation, Detroit 48201, USA.
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011230:Precancerous Conditions / Q000473:pathology*; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen