Question

1. What sorts of mutational changes could occur in a gene for a cyclin-dependent kinase might lead to a cell becoming cancerous? Be as specific as you can as to what effect the mutational change would have on the kinase protein.

Answer 1

Gene amplification or a chromosome translocation that places cyclin D1 under control of an inappropriate promoter leads to overexpression of this cyclin in many human cancers, indicating that it can function as an oncoprotein. In certain tumors of the antibody-producing B cells, for instance, the cyclin D1 gene is translocated such that its transcription is under control of an antibody-gene enhancer, causing elevated cyclin D1 production throughout the cell cycle irrespective of extracellular signals. (This phenomenon is analogous to the c-myc translocation in Burkitt’s lymphoma cells discussed earlier.) Cyclin D1 overexpression can directly cause cancer was shown by studies with a transgenic mouse in which the cyclin D gene was placed under control of an enhancer specific for mammary ductal cells. Initially the ductal cells underwent hyperproliferation, and eventually breast tumors developed in these transgenic mice. Amplification of the cyclin D1 gene and concomitant overexpression of the cyclin D1 protein is common in human breast cancer.