Mammary epithelial cells immortalized by over-expression of the catalytic subunit of human telomerase may represent a model for mammary epithelial differentiation

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Retroviral transfer of a cDNA encoding human Telomeric End Reverse Transcriptase (hTERT) into primary human mammary epithelia has led to the establishment of several clonally derived lines of Immortalized Mammary Epithelial Cells (IMECs). Unlike their empty vector control counterparts, the IMECs were capable of bypassing replicative senescence. In doing so, they exhibited a marked decrease in the protein levels of the retinoblastoma gene product, Rb, and a complete loss of the cyclin-dependent kinase inhibitor p16, events which are hallmarks of the immortalization process. In culture, IMECs proliferate in a manner that is dependent on insulin and Epidermal Growth Factor (EGF). Interestingly, these IMECs can be induced to undergo a differentiation which is characterized by an arrest of the cell cycle in G1 and the loss of cyclin D1 expression. During this differentiation process, IMECs establish cell-cell interactions that lead to an ordered arrangement of cells in two dimensions. Further genetic and biochemical characterization may hopefully reveal the nature of these differentiated IMECs.