Transcription factors and breast cancer

¹ Department of Medicine, University of California at San Francisco, California 94143, USA

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.

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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.