Abstract
The mammary gland in adult women consists of biologically distinct cell types that differ in their surface phenotypes. Isolation and molecular characterization of these subpopulations of mammary cells have provided extensive insights into their different transcriptional programs and regulation. This information is now serving as a baseline for interpreting the heterogeneous features of human breast cancers. Examination of breast cancer mutational profiles further indicates that most have undergone a complex evolutionary process even before being detected. The consequent intra‐tumoral as well as inter‐tumoral heterogeneity of these cancers thus poses major challenges to deriving information from early and hence likely pervasive changes in potential therapeutic interest. Recently described reproducible and efficient methods for generating human breast cancers de novo in immunodeficient mice transplanted with genetically altered primary cells now offer a promising alternative to investigate initial stages of human breast cancer development. In this review, we summarize current knowledge about key transcriptional regulatory processes operative in these partially characterized subpopulations of normal human mammary cells and effects of disrupting these processes in experimentally produced human breast cancers.
Highlights
A variety of technologies have been used over the past 10 years to characterize the transcriptomes of basal cells (BCs), luminal progenitors (LPs), and luminal cells (LCs) isolated from normal adult female breast tissue (Bloushtain-Qimron et al, 2008; Raouf et al, 2008; Lim et al, 2009, 2010; Maruyama et al, 2011; Shehata et al, 2012; Kannan et al, 2013; Gascard et al, 2015; Pellacani et al, 2016)
The invasive nature of the primary clones but their general lack of perpetuation in secondary implants contrasts with the conventional concept of the oncogenic process, in which the control of invasive properties by human mammary cells is usually modeled as property that is acquired after deregulated growth has created a large “premalignant” population from which a more advanced derivative arises
Heterogeneity is a pronounced feature of human breast cancer genomes and epigenomes
Summary
A variety of technologies have been used over the past 10 years to characterize the transcriptomes of BCs, LPs, and LCs isolated from normal adult female breast tissue (Bloushtain-Qimron et al, 2008; Raouf et al, 2008; Lim et al, 2009, 2010; Maruyama et al, 2011; Shehata et al, 2012; Kannan et al, 2013; Gascard et al, 2015; Pellacani et al, 2016) These studies have revealed consistent differences in the activity of hundreds of genes in each of these phenotypically defined subsets.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
