Abstract
During the formation of breast cancer, many genes become altered as cells evolve progressively from normal to a pre-malignant to a malignant state of growth. How mutations in genes lead to specific subtypes of human breast cancer is only partially understood. Here we review how initial genetic or epigenetic alterations within mammary epithelial cells (MECs) can alter cell fate decisions and put pre-malignant cells on a path towards cancer development with specific phenotypes. Understanding the early stages of breast cancer initiation and progression and how normal developmental processes are hijacked during transformation has significant implications for improving early detection and prevention of breast cancer. In addition, insights gleaned from this understanding may also be important for developing subtype-specific treatment options.
Highlights
IntroductionOver the past three decades, enormous strides have been made in understanding the genetic and biochemical defects in cancer cells that are responsible for deregulated growth and proliferation
Over the past three decades, enormous strides have been made in understanding the genetic and biochemical defects in cancer cells that are responsible for deregulated growth and proliferation.Research has revealed critical mutations in many key cellular genes, oncogenes and tumor suppressor genes, within the genomes of a wide variety of human breast cancer cells
We focus on work that has identified the cell-of-origin for various breast cancer subtypes and how cell fate changes in different precursor cells leads to tumors with different phenotypes and behaviors
Summary
Over the past three decades, enormous strides have been made in understanding the genetic and biochemical defects in cancer cells that are responsible for deregulated growth and proliferation. During the formation of the majority of breast cancers, these genes become altered as cells evolve progressively from normal to a pre-malignant to a malignant state of growth These findings have been most illustrative, they fail to inform us about the details of how specific subtypes of human breast cancer begin. We focus on work that has identified the cell-of-origin for various breast cancer subtypes and how cell fate changes in different precursor cells leads to tumors with different phenotypes and behaviors. This new understanding has significant implications for early detection and prevention of breast cancer, as well as possible development of improved therapeutics unique for each tumor subtype. Biol. 2016, 4, 4 breast cancer formation, much remains to be uncovered regarding how the cell-of-origin responds to mutation, stress, DNA damage and aging
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