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Rho GDIα and Tamoxifen Resistance

Tamoxifen has widely been used as adjuvant treatment for estrogen receptor (ER)-positive breast cancer, but patients sometimes become resistant to the drug. Barone et al. (p. 538 ) used microarrays to look for genes associated with tamoxifen resistance in breast cancer samples. Tamoxifen-resistant tumors had lower levels of Rho GDIα gene expression compared with responsive tumors. ER-positive MCF-7 breast cancer cells in which Rho GDIα expression was silenced were tamoxifen-resistant and had both increased Rho signaling and tamoxifen-induced ERα transcriptional activity compared with parental cells. They also formed tumors that, unlike parental cells, metastasized readily when implanted into mice. Preliminary findings showed that human breast tumors with low Rho GD1α and high MTA2 expression were more likely to be tamoxifen-resistant.

In an editorial, Van Tine and Ellis (p. 526 ) point out that these authors’ findings are accompanied by both confirmatory and conflicting evidence from the literature. Multiple pathways may lead to tamoxifen resistance, and further association of genomic changes with clinical outcomes will be key to figuring it all out, they say.