Molecular Biology

Acting Out of Character

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Science  05 Mar 2010:
Vol. 327, Issue 5970, pp. 1180
DOI: 10.1126/science.327.5970.1180-b

The steroid receptor coactivator 3 gene, SRC-3, was identified in a region on chromosome 20 that was frequently amplified in breast cancer. The SRC-3 protein was shown to act in the nucleus to regulate the transcription of genes involved in growth and development. Long et al. report that the SRC-3 transcript can undergo alternative splicing to produce two proteins with distinct personalities. In comparison to the full-length protein, SRC-3Δ4 lacks exon 4, which encodes the DNA-binding domain and a nuclear localization signal. Like SRC-3, the SRC-3Δ4 isoform is overexpressed in breast cancer and other tumors, but it localizes to the plasma membrane and acts as a cytoplasmic signaling coactivator by mediating epidermal growth factor (EGF)–induced cell migration. SRC-3Δ4 couples the EGF receptor to one of its downstream signaling effectors, focal adhesion kinase. EGF is known to promote cancer cell migration and metastasis, and overexpression of SRC-3Δ4 in breast cancer cells induced metastasis to the lymph node and lung in mice. Thus, both SRC-3 and its close relative SRC-3Δ4 are linked to breast cancer, but likely via completely distinct pathways.

Mol. Cell 37, 321 (2010).

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