DHEA increases epithelial markers and decreases mesenchymal proteins in breast cancer cells and reduces xenograft growth.

Breast cancer is one of the most common neoplasias and the leading cause of cancer death in women worldwide. Its high mortality rate is linked to a great metastatic capacity associated with the epithelial-mesenchymal transition (EMT). During this process, a decrease in epithelial proteins expression and an increase of mesenchymal proteins are observed. On the other hand, it has been shown that dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, inhibits migration of breast cancer cells; however, the underlying mechanisms have not been elucidated. In this study, the in vitro effect of DHEA on the expression pattern of some EMT-related proteins, such as E-cadherin (epithelial), N-cadherin, vimentin and Snail (mesenchymal) was measured by Western blot and immunofluorescence in MDA-MB-231 breast cancer cells with invasive, metastatic and mesenchymal phenotype. Also, the in vivo effect of DHEA on xenograft tumor growth in nude mice (nu-/nu-) and on expression of the same epithelial and mesenchymal proteins in generated tumors was evaluated. We found that DHEA increased expression of E-cadherin and decreased N-cadherin, vimentin and Snail expression both in MD-MB-231 cells and in the formed tumors, possibly by DHEA-induced reversion of mesenchymal phenotype. These results were correlated with a tumor size reduction in mouse xenografts following DHEA administration either a week earlier or concurrent with breast cancer cells inoculation. In conclusion, DHEA could be useful in the treatment of breast cancer with mesenchymal phenotype.

Colín-Val Z ，González-Puertos VY ，Mendoza-Milla C ，Gómez EO ，Huesca-Gómez C ，López-Marure R ... -  《-》

Mouse double minute 2 (MDM2) upregulates Snail expression and induces epithelial-to-mesenchymal transition in breast cancer cells in vitro and in vivo.

Lu X ，Yan C ，Huang Y ，Shi D ，Fu Z ，Qiu J ，Yin Y ... -  《Oncotarget》

DHEA inhibits proliferation, migration and alters mesenchymal-epithelial transition proteins through the PI3K/Akt pathway in MDA-MB-231 cells.

Cancer is one of the leading causes of death worldwide, and breast cancer is the most common among women. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone in human serum, inhibits proliferation and migration of breast cancer cells, modulating the expression of proteins involved in mesenchymal-epithelial transition (MET). However, the underlying molecular mechanisms are not fully understood. DHEA effects on the triple-negative breast cancer cell line MDA-MB-231 (mesenchymal stem-like) could be exerted by binding to receptors tyrosine kinase (RTKs) and signaling through MEK/ERK and/or PI3K/Akt pathways. In this study, MDA-MB-231 cells were exposed to DHEA in the presence of pharmacological inhibitors of these pathways and a siRNA against PIK3CA gene, which blocks PI3K pathway. Cell proliferation was measured by crystal violet staining, migration by the wound healing and transwell assays, and MET protein expression by western blot. A xenograft tumor growth in nude mice (nu-/nu-) using a siRNA against PI3K was also performed. Results showed that neither of the inhibitors used reverted the antiproliferative activity of DHEA. However, wortmannin and LY294002, inhibitors of the PI3K/Akt pathway, abolished the up- and down-regulation of E- and N-cadherin expression respectively, and inhibition of migration induced by DHEA in MDA-MB-231 cells. The siRNA that blocks the PI3K pathway, abolished the effects of DHEA on proliferation, migration, MET proteins expression and the growth of tumors in nude mice. In conclusion, these results suggest that PI3K/Akt pathway participates in the effects of DHEA on breast cancer cells.

Colín-Val Z ，López-Díazguerrero NE ，López-Marure R 《-》

Epithelial to mesenchymal transition is associated with rapamycin resistance.

Holder AM ，Akcakanat A ，Adkins F ，Evans K ，Chen H ，Wei C ，Milton DR ，Li Y ，Do KA ，Janku F ，Meric-Bernstam F ... -  《Oncotarget》

Epithelial requirement for in vitro proliferation and xenograft growth and metastasis of MDA-MB-468 human breast cancer cells: oncogenic rather than tumor-suppressive role of E-cadherin.

Hugo HJ ，Gunasinghe NPAD ，Hollier BG ，Tanaka T ，Blick T ，Toh A ，Hill P ，Gilles C ，Waltham M ，Thompson EW ... -  《-》