An Integrated Human Mammary Epithelial Cell Culture System for Studying Carcinogenesis and Aging

摘要: Experimental examination of the agents and processes that may propel or prevent human breast carcinogenesis can be facilitated by in vitro model systems transformation, starting with normal cells, accurately reflect vivo biology. Model replicate types alterations seen during progression offer potential to understand mechanisms underlying examine possible means individualized prevention treatment. To this end, we have developed an experimentally tractable mammary epithelial cell (HMEC) culture system has been used governing HMEC growth, differentiation, aging, senescence how these are altered immortal malignant transformation. Isogenic cells at different stages multistep were generated exposing finite lifespan a variety oncogenic play etiologic role cancer. Examination molecular present each stage indicated is consistent observed vivo. We varying target type, used, lead multiple distinct pathways although full diversity cancer not yet models. Using integrated system, formulated comprehensive proliferative barriers must overcome gain immortality malignancy. Our data provide insights on acquisition cancer-associated properties suggest most crucial step involves transition from indefinite lifespan. For example, see genomic instability originates when telomeres become critically short engage telomeric associations then maintained resultant immortalized lines. Direct targeting tumor-suppressive produce lines lacking gross errors, supporting hypothesis mechanism generate cancer-causing but necessary per se. Immortalization through telomerase reactivation was also associated resistance TGFβ growth inhibition oncogene-induced (OIS) large-scale changes gene expression epigenetic marks. Being able progressive fuel malignancy, provides perspective reveal novel information origins consequences individual aberrations.