It has been almost a quarter century since it was first appreciated that a class of oncogenes contained in rapidly transforming avian retroviruses encoded
DNA-binding
transcription factors. As with other oncogenes, genetic recombination with the viral genome led to their overexpression or functional alteration. In the years that followed, alterations of numerous
transcription factors were shown to be causatively involved in various
cancers in human patients and model organisms. Depending on their normal cellular functions, these factors were subsequently categorized as proto-oncogenes or tumor suppressor genes. This review focuses on the role of
GATA transcription factors in
carcinogenesis.
GATA factors are zinc finger
DNA binding proteins that control the development of diverse tissues by activating or repressing transcription.
GATA factors thus coordinate cellular maturation with proliferation arrest and cell survival. Therefore, a role of this family of genes in human
cancers is not surprising. Prominent examples include structural mutations in GATA1 that are found in almost all megakaryoblastic
leukemias in patients with
Down syndrome; loss of GATA3 expression in aggressive, dedifferentiated breast
cancers; and silencing of GATA4 and GATA5 expression in colorectal and
lung cancers. Here, we discuss possible mechanisms of
carcinogenesis vis-à-vis the normal functions of
GATA factors as they pertain to human patients and mouse models of
cancer.