Malignancy: an evolving definition of a cancer cell.

Abstract

1. J Lynne Williams, PhD[⇑][1] 1. is Professor, Medical Laboratory Sciences School of Health Sciences, Oakland University, Rochester MI 1. Address for correspondence: J Lynne Williams Professor, Med Lab Sciences, Oakland University, Rochester MI 48309. (734) 647-2898 or (248) 370-4040. lynnew{at}umich.edu or jlwillia{at}oakland.edu 1. Compare and contrast the functional characteristics of oncogenes and tumor suppressor genes. 2. Summarize the four broad functional categories of oncogenes. 3. Define and explain the role of cyclins and Cdks in regulating cell cycle progression. 4. Describe the ‘cell-cycle checkpoints’. 5. Explain how loss of Rb protein can contribute to oncogenesis. 6. Summarize the roles of caspases, the Bcl-2 family of proteins, and IAPs (inhibitors of apoptosis) in the regulation of apoptosis. 7. Correlate overexpression of Bcl-2 and Bcl-XL, or loss of function of p16 or p27, with oncogenesis. 8. Describe the role of telomerase in tumorigenesis. In recent years there has been an explosive growth in our understanding of cancer cell biology. For most of the 20th century, cancer was assumed to be a disease of uncontrolled proliferation of cells. A (malignant) neoplasm was defined as ‘an abnormal mass of cells typically exhibiting uncontrolled and progressive growth’.1 A more current definition of malignancy recognizes the complex interplay of an imbalance between cell proliferation, differentiation, and cell death.2 The molecular mechanisms regulating cell proliferation and cell death (apoptosis) have been among the areas of biomedical research generating intense interest for the past 20 years. As these molecular controls have been defined and refined, our understanding of the molecular basis of malignancy has similarly been advanced, and new diagnostic and therapeutic approaches for various human malignancies are being developed. ONCOGENES AND TUMOR SUPPRESSOR GENES Cancer is a genetic disease. The characteristics that make a cell malignant are stably inherited during the process of cell division. We also recognize that most tumors are clonally derived from a single common progenitor cancer cell that typically divides to generate a tumor of identical sibling cells. Together, these two observations indicate that the disease phenotype is determined by the tumor cell DNA. A major advancement in understanding cancer cell biology was the discovery that certain viruses, when inoculated into animals, had the capacity to cause the development of tumors. This critically important observation resulted in a massive investigation to identify the particular viral genes capable of inducing malignant transformation. The tumor-causing viruses… ABBREVIATIONS: Cdk = cyclin-dependent kinases; PTK = protein-tyrosine kinases. 1. Compare and contrast the functional characteristics of oncogenes and tumor suppressor genes. 2. Summarize the four broad functional categories of oncogenes. 3. Define and explain the role of cyclins and Cdks in regulating cell cycle progression. 4. Describe the ‘cell-cycle checkpoints’. 5. Explain how loss of Rb protein can contribute to oncogenesis. 6. Summarize the roles of caspases, the Bcl-2 family of proteins, and IAPs (inhibitors of apoptosis) in the regulation of apoptosis. 7. Correlate overexpression of Bcl-2 and Bcl-XL, or loss of function of p16 or p27, with oncogenesis. 8. Describe the role of telomerase in tumorigenesis. [1]: #corresp-1