Oncogenic and Tumor Suppressive Components of the Cell Cycle in Breast Cancer Progression and Prognosis

Cancer, a disease of inappropriate cell proliferation, is strongly interconnected with the cell cycle. All cancers consist of an abnormal accumulation of neoplastic cells, which are propagated toward uncontrolled cell division and proliferation in response to mitogenic signals. Mitogenic stimuli include genetic and epigenetic changes in cell cycle regulatory genes and other genes which regulate the cell cycle. This suggests that multiple, distinct pathways of genetic alterations lead to cancer development. Products of both oncogenes (including cyclin-dependent kinase (CDKs) and cyclins) and tumor suppressor genes (including cyclin-dependent kinase inhibitors) regulate cell cycle machinery and promote or suppress cell cycle progression, respectively. The identification of cyclins and CDKs help to explain and understand the molecular mechanisms of cell cycle machinery. During breast cancer tumorigenesis, cyclins A, B, C, D1, and E; cyclin-dependent kinase (CDKs); and CDK-inhibitor proteins p16, p21, p27, and p53 are known to play significant roles in cell cycle control and are tightly regulated in normal breast epithelial cells. Following mitogenic stimuli, these components are deregulated, which promotes neoplastic transformation of breast epithelial cells. Multiple studies implicate the roles of both types of components-oncogenic CDKs and cyclins, along with tumor-suppressing cyclin-dependent inhibitors-in breast cancer initiation and progression. Numerous clinical studies have confirmed that there is a prognostic significance for screening for these described components, regarding patient outcomes and their responses to therapy. The aim of this review article is to summarize the roles of oncogenic and tumor-suppressive components of the cell cycle in breast cancer progression and prognosis.

Automated summary

Cancer, a disease of inappropriate cell proliferation, is closely linked to the cell cycle, with multiple genetic alterations leading to cancer development. Both oncogenes and tumor suppressor genes regulate the cell cycle and play key roles in breast cancer progression. These components are tightly controlled in normal breast epithelial cells, but following mitogenic stimuli, their deregulation promotes neoplastic transformation. Numerous clinical studies have revealed prognostic significance in screening for these components, impacting patient outcomes and treatment responses. The review aims to summarize the roles of oncogenic and tumor-suppressive components in breast cancer progression and prognosis.