Brain-metastatic triple-negative breast cancer cells regain growth ability by altering gene expression patterns.

UNLABELLED: BACKGROUD/AIM: Triple-negative breast cancer (TNBC) frequently metastasizes to the brain (BrM). However, genes responsible for BrM of TNBC are yet to be identified. MATERIALS AND METHODS: Gene expression profiling of TNBC and BrM was conducted, and studies with cultured cells in vitro were performed to verify functions of genes identified in these analyses. RESULTS: According to gene expression analyses of TNBC and BrM, periplakin (PPL) and mitogen-activated protein kinase 13 (MAPK13) were chosen for further investigations. PPL and MAPK13 were highly expressed in TNBC compared to BrM. While silencing of either PPL or MAPK13 in TNBC cells increased cell growth and reduced cell motility, overexpression of either PPL or MAPK13 in BrM cells, retarded growth rates and facilitated cell motility. CONCLUSION: Gene expression patterns in TNBC and BrM reflect cancer cell growth in regions of metastasis.

Cloning and expression of an SH3 domain-containing protein (Xchef-1), a novel downstream target of activin/nodal signaling.

The activity of the activin/nodal signaling cascade is essential for the proper specification of germ layers during gastrulation. Many of the components of this signaling pathway have been identified, but relatively few downstream targets have been discovered. Using cDNA microarrays, we have identified a novel SH3-domain-containing gene we have named Xchef-1 that is upregulated in response to activin/nodal signaling. Xchef-1 is a direct downstream target of activin and is expressed in the marginal zones of gastrulating Xenopus embryos in a dynamic pattern reminiscent of nodal expression. At neurula stages, Xchef-1 is expressed in neural crest of the head and trunk as well as in the anterior neural plate. These domains of expression are then restricted at tailbud stages to the branchial arches, and the region of the future gall bladder.