Pharmaceutica Analytica Acta

Abstrato

Alteration in Transcriptional State, as a First Step in Cancer Development

Uchiumi F, Larsen S and Tanuma S

Abstract
The risk of cancer, which increases in accordance with aging, has been mainly explained by the oxidative stresses that cause DNA damage. In fact, recent DNA sequencing studies of genomes from cancer patients revealed a variety of mutations on specific genes, suggesting that accumulation of DNA damage is the main cause for development of cancer. Therefore, great effort has been undertaken to analyze DNA mutations. On the other hand, especially for clinical diagnosis, abnormalities in metabolism, including up-regulation of glycolysis or “Warburg effect”, are known to be characteristics of cancer. Taken together, cancer could be referred to as both “genetic disease” and a “metabolic disease”. We have confirmed that numbers of DNA-repair- and mitochondrial function-associated gene promoters commonly contain a duplicated GGAA-motif, which is a target for multiple transcription factors. In this article, we will tentatively draw a hypothetical mechanism behind the generation of cancerous cells, in which alterations in transcriptional state have occurred primarily with repeated divisions or aging of normal cells. Thus, cancer could be regarded as a “transcriptional disease”. We hope this concept contribute for innovation of a new cancer therapeutics targeting transcription.