Transcription factors and breast cancer

Transcription factors are gene regulatory proteins endowed with sequence-specific DNA recognition and the ability to positively or negatively influence the rate and efficiency of transcript initiation at a gene containing the factor's cognate recognition sequence, or DNA response element. Since transcription factors lie at the heart of almost every fundamental developmental and homeostatic organismal process- including DNA replication and repair, cell growth and division, control of apoptosis and cellular differentiation- it is not surprising that inherited or acquired defects in transcription factor structure and function contribute to human carcinogenesis. As of 6 years ago a comprehensive list included greater than 150 well characterized vertebrate transcription factors (Faisst and Meyer; 1992); individual families of transcription factors such as the Ets family, composed of only a few known members at that time, have since grown to include greater than 30 members (Wasylyk and Nordheim; 1997). Furthermore, many of these same gene stimulating or repressing factors have been shown to have oncogenic properties when genomically altered (mutated, rearranged, amplified or deleted), transcriptionally upregulated, or post-translationally modified. Thus, we have come to realize that this growing body of transcription factors and the development-specific and tissue-restricted gene programs under their control represent a rich and diverse source of mechanisms which, if disrupted, can lead to various types of malignancy including breast cancer. Acknowledgements This review is dedicated to the memory of Dr Helene Smith - a rigorous scientist, compassionate leader, and tireless champion of new ideas and efforts to understand and conquer breast cancer. This work was supported in part by NIH sponsored grants P01-CA44768, R01-CA36773, and R01-CA-71468 as well as the Hazel P Munroe and Janet Landfear memorial funds.