Chapters authored
Early-Stage Progression of Breast Cancer
Breast cancer can be defined as a group of diseases with heterogeneous origins, molecular profiles and behaviors characterized by uncontrolled proliferation of cells within the mammary tissue. Around one in eight women in the US will develop breast cancer in their lifetime, making it the second most frequently diagnosed cancer behind skin cancer [1]. In 2015, an estimated 231,840 cases of invasive carcinoma were diagnosed, and over 40,000 deaths were caused by breast cancer which accounts for almost 7% of all cancer mortality each year. In 2015, 60,290 cases of in situ breast cancer were diagnosed, representing over 14% of all new cancer cases among women and men. The steep increase in diagnosis of early‐stage breast cancer over the past 10 years is believed to be a result of more frequent mammography. However, since over half of these in situ lesions will not progress to invasive breast cancer, controversies have arisen about approaches to treatment and prevention of progression of early‐stage in situ breast cancer. Understanding the mechanisms of transition of normal breast to in situ pre‐neoplastic lesions and invasive breast cancer is currently a major focus of breast cancer research with implications for preventive and clinical management of breast cancer. In this review, we give an overview of current knowledge on the molecular and pathological changes that occur during early‐stage progression of breast cancer and describe some of the current models that are used to study this process.
Part of the book: Breast Cancer
The AIB1/NCOA3/SRC-3 Oncogene
A member of the NCOA/SRC/p160 co-activator family, AIB1 is amplified and overexpressed in multiple cancer types, notably breast, ovarian, and pancreatic cancer. Common to all members of the NCOA/SRC/p160 family are bHLH-PAS, receptor interaction, and CBP/p300 interacting activation domains. The protein acts as a scaffold to support the transcriptional activity of many DNA binding transcription factors, such as the ER, AP-1, E2F, NFκB, and TEADs. In doing so, the multi-domain protein facilitates chromatin remodeling and oncogenic gene transcription. Further, the AIB1Δ4 isoform promotes tumorigenesis and metastasis through interaction with chromatin in the nucleus or at the periphery of the cell. Pathologically, AIB1 promotes the transformation of normal tissue to cancerous lesions in multiple diseases, and loss delays progression. AIB1 has also been implicated in cancer recurrence and pharmacological resistance. We will discuss the structure and isoforms of AIB1, the physiological consequences of its interaction with transcription factors and hormone receptors, and clinical significance of the protein.
Part of the book: Oncogenes and Carcinogenesis