Editorial [Hot Topic: Transription Factors and their Modulated Genes as Targets for Chemoprevention (Guest Editor: Chuanshu Huang)]

Cancer development is recognized as a multi-stage phenomenon consisting of initiation, promotion and progression stages. The rate-limiting steps in multistage carcinogenesis are now thought to reside during the period of tumor promotion and progression. Exposure to tumor promoters results in activation of transcription factors, and regulation of their target genes through signal transduction pathways, which have been characterized as tumor promotion and progression stages. Therefore, one of the most difficult challenges for scientists in the cancer research field is addressing fundamental questions concerning the response of mammalian cells to carcinogens at the level of transcription factors and protein kinases both in vitro and in vivo. Elucidation of carcinogeninduced signal transduction pathways leading to the activation of transcription factors by which gene expression is mediated will therefore, not only define the central scientific hunt in cancer biology and open an unprecedented window into the nature of cancer, but will also be necessary for cancer prevention and therapy as well. Chemoprevention can be defined as the use of substances that interfere with the process of cancer development. Since cancer is a multifactor disease that requires the modulation of multiple pathways, chemoprevention could target multiple targets. These targets include transcription factors, kinase cascades leading to activation, as well as downstream target genes of those transcription factors. Although substantial progress has been made in elucidating signal transduction pathways leading to the activation of transcription factors induced by carcinogens, further advances are needed to identify molecular targets for effective use of chemopreventive agents. This special issue describes the most recent progress made in this field. The PI3K/Akt signaling pathway is a relative early event involved in the mediation of the activation of its downstream transcription factors. Growing evidence demonstrates that dysregulation of this pathway is critical for the carcinogenic effect upon environmental carcinogen exposure. The first review article provided by Dr. Huang and his colleague summarizes the PI3K/Akt pathway, its downstream regulated transcriptional factors, and the dysregulation of this pathway in carcinogenesis, as well as the chemoprevention strategies targeting those components. The transcription factor activator protein-1 (AP-1) plays a pivotal role in inflammation and tumorigenesis, which has been supported in research both in vitro and in vivo. AP-1 could also act as a link between chronic inflammation and tumor development. The second review by Drs. Matthews, Colburn and Young has addressed the AP-1 family proteins, its relation to inflammation and cancer development, and as targets for chemoprevention. More than 1,000,000 cases of non-melanoma skin cancer (NMSC) are diagnosed in the Unites States each year. Solar radiation has been described as an important etiological factor in the development of NMSC. Damage of cells induced by ultraviolet B (UVB) light at the DNA level and molecular level initiates the activation of transcription factor pathways, which in turn, regulate the expression of a number of genes termed the “UV response genes”. Nuclear factor-κB (NF-κB) and AP-1 are two important transcription factors that are responsible for the regulation of those response genes. The review from Dr. Bowden's group has extensively discussed the advances made in this research area. Ionizing radiation (IR) is another environmental carcinogenic factor. Dr. Li's review article has focused on recent findings related to the relationship between ATM and NF-κB in response to IR, and the association of ATM with the NF-κB subunit p65 in adaptive radiation response as well. Nuclear factor of activated T cells (NFAT) is another important family of transcription factors which have important roles in various cell functions. In the last a few years, there has been increasing evidence relating NFAT family proteins to carcinogenesis, even though various members may have different roles...