Global MicroRNA Expression Profiling Identifies MiR-210 Associated with Tumor Proliferation, Invasion and Poor Clinical Outcome in Breast Cancer

Aberrant microRNA (miRNA) expression is associated with cancer and has potential diagnostic and prognostic value in various malignancies. In this study, we investigated miRNA profiling as a complementary tool to improve our understanding of breast cancer (BC) biology and to assess whether miRNA expression could predict clinical outcome of BC patients.In VitroJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Steroid-free medium discloses oestrogenic effects of the bisphosphonate clodronate on breast cancer cells

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Homocamptothecin, an E-ring-modified camptothecin, exerts more potent antiproliferative activity than other topoisomerase I inhibitors in human colon cancers obtained from surgery and maintained in vitro under histotypical culture conditions.

Topoisomerase I (Topo I) is overexpressed in cancer colon tissues compared with normal colon tissues. Several anti-Topo I inhibitors are already successfully used in the clinic. We illustrate here the antiproliferative activity of a new class of Topo I inhibitors, i.e. E-ring-modified camptothecins with enhanced lactone stability (L. Lesueur-Ginot et al. Cancer Res. 59: 2939-2943, 1999). Forty-three human colon cancers were obtained from surgical resection and maintained under organotypical culture conditions for 48 h. Cell proliferation was assessed in these ex vivo tumor tissue cultures by tritiated thymidine autoradiography. As a validation of the methodology, we first analyzed in our model the antiproliferative activity of two clinically active topoisomerase II (Topo II) inhibitors, Adriamycin and etoposide, which are not active for colon cancers; and three Topo I inhibitors, camptothecin (CPT) and two clinically active compounds (especially for colon cancers), i.e. topotecan and the active metabolite of irinothecan, SN-38. We then compared the antiproliferative activity of CPT, topotecan, and SN-38 against those of two investigational E-ring-modified camptothecins, i.e. BN80245 and BN80915. Three concentrations (1, 10, and 100 nM) were studied for each compound. The results indicate that the three Topo I inhibitors used as references, i.e. CPT, irinothecan, and SN-38, were much more active than the two Topo II inhibitors, i.e. Adriamycin and etoposide, with SN-38 being the most efficient. The two investigational compounds BN80245 and BN80915 exerted higher antiproliferative activity than the three anti-Topo I reference compounds, with the highest activity observed for BN80915.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Association between farnesoid X receptor expression and cell proliferation in estrogen receptor-positive luminal-like breast cancer from postmenopausal patients.

The farnesoid X receptor (FXR, NR1H4), a member of the nuclear receptor superfamily of ligand-dependent transcription factors, is normally produced in the liver and the gastrointestinal tract, where it acts as a bile acid sensor. It has been recently detected in breast cancer cell lines and tissue specimens. The expression of FXR was scored (0-8) by immunohistochemistry on 204 breast cancer samples and correlated with established cancer biomarkers. Moreover, the effect of the FXR activator chenodeoxycholic acid (CDCA) was determined on cell proliferation and estrogen receptor regulation/activation in breast cancer cell lines. FXR was detected in 82.4% of samples with a high median expression score of 5. FXR expression significantly correlated with estrogen receptor (ER) expression (P = 0.009) and luminal-like markers. In ER-positive tumors, FXR expression was significantly correlated with the proliferation marker Ki-67 (P < 0.001) and the nodal status (P = 0.028), but only so in postmenopausal women, suggesting that lack of estrogens may disclose the association between FXR and cell proliferation. In vitro experiments confirmed clinical data since CDCA stimulated the proliferation of ER-positive cells only in steroid-free medium, a stimulation inhibited upon siRNA-silencing of FXR expression as well as ER blockade by antiestrogens. Moreover, co-immunoprecipitation experiments revealed that CDCA activated-FXR interacted with ER. These results suggest that ER-positive breast tumors could be stimulated to proliferate via a crosstalk between FXR and ER, particularly in a state of estrogen deprivation (menopause, aromatase inhibitors).Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe