GATA Differentiate!

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Science  29 Feb 2008:
Vol. 319, Issue 5867, pp. 1162
DOI: 10.1126/science.319.5867.1162a

Because most cancer deaths are due to metastatic disease, there is great interest in developing therapies that would prevent cells in a primary tumor from undergoing the changes that confer the capacity to disseminate, or that would reverse such changes. Tumors that are destined to disseminate and metastasize display molecular markers that distinguish them from less aggressive cells, but it is not clear if these molecules play a causal role in tumor metastasis, and hence would be suitable drug targets.

Kouros-Mehr et al. have explored the role of one intriguing predictive marker in human breast cancer, a transcription factor called GATA-3 that is required for the differentiation and proper function of normal mammary tissue. Breast tumors with low expression levels of GATA-3 typically are poorly differentiated, have a higher metastatic potential, and are associated with a worse clinical outcome than are tumors with high levels of GATA-3. Studying a mouse model of breast cancer, the authors found that GATA-3 expression and markers of differentiated epithelial cells (red-yellow) were lost very early in tumor progression and that this loss was likely due to the expanded growth of GATA-3-negative mammary stem cells (blue). Importantly, when they reintroduced GATA-3-positive cells into later-stage breast tumors, the tumors became more differentiated and showed a reduced capacity to disseminate. These results indicate that GATA-3 is not only a marker but also a causal factor in tumor metastasis, and that drugs activating GATA-3 itself or the molecules that regulate it could form the basis of differentiation therapy for breast cancer. — PAK

Cancer Cell 13, 141 (2008).

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