The nucleolar aspect of breast cancer

Abstract

The oncogenic process of breast cancer is associated with significant morphological and metabolic changes. One aspect of these changes occur in the nucleolus. The nucleolus is the major structure of the nucleus and is responsible for ribosome biosynthesis. Production of pre-rRNA is mediated by RNA polymerase I (Pol I). Pol I-mediated transcription of approximately 200 copies of transcriptionally active rDNA repeats constitutes approximately 60% of nuclear transcription activity. Therefore, the rate of ribosome synthesis in the nucleoli dictates cell proliferation. The upregulation of cell proliferation is a vital aspect of tumorigenesis, including mammary tumorigenesis. While breast cancer forms a group of heterogeneous diseases that are associated with different clinical outcomes, high proliferation rate predicts poor prognosis for all subtypes of breast cancers. In agreement with the above concepts, abnormalities in the number, size, and morphology of nucleoli are generally associated with breast cancer initiation and progression. Furthermore, factors and/or pathways, i.e. tumour suppressors and oncogenes, which regulate mammary tumorigenesis also takes control of ribosome biosynthesis in the nucleoli. In this chapter we will summarize the current understanding of the relationship between nucleoli and breast tumorigenesis.