{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:29:30Z","timestamp":1791268170211,"version":"4.1.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,11,25]],"date-time":"2010-11-25T00:00:00Z","timestamp":1290643200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2010,11,25]],"date-time":"2010-11-25T00:00:00Z","timestamp":1290643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2010,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n The\n DLX<\/jats:italic>\n gene family encodes for homeobox transcription factors involved in the control of morphogenesis and tissue homeostasis. Their expression can be regulated by Endothelin1 (ET1), a peptide associated with breast cancer invasive phenotype. Deregulation of\n DLX<\/jats:italic>\n gene expression was found in human solid tumors and hematologic malignancies. In particular,\n DLX4<\/jats:italic>\n overexpression represents a possible prognostic marker in ovarian cancer. We have investigated the role of\n DLX<\/jats:italic>\n genes in human breast cancer progression.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n MDA-MB-231 human breast carcinoma cells were grown in vitro or injected in nude mice, either subcutaneously, to mimic primary tumor growth, or intravenously, to mimic metastatic spreading. Expression of\n DLX2<\/jats:italic>\n ,\n DLX5<\/jats:italic>\n and\n DLX6<\/jats:italic>\n was assessed in cultured cells, either treated or not with ET1, tumors and metastases by RT-PCR.\n In situ<\/jats:italic>\n hybridization was used to confirm\n DLX<\/jats:italic>\n gene expression in primary tumors and in lung and bone metastases. The expression of\n DLX2<\/jats:italic>\n and\n DLX5<\/jats:italic>\n was evaluated in 408 primary human breast cancers examining the GSE1456 and GSE3494 microarray datasets. Kaplan-Meier estimates for disease-free survival were calculated for the patients grouped on the basis of\n DLX2<\/jats:italic>\n \/\n DLX5<\/jats:italic>\n expression.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Before injection, or after subcutaneous growth, MDA-MB-231 cells expressed\n DLX2<\/jats:italic>\n but neither\n DLX5<\/jats:italic>\n nor\n DLX6<\/jats:italic>\n . Instead, in bone and lung metastases resulting from intravenous injection we detected expression of\n DLX5\/6<\/jats:italic>\n but not of\n DLX2<\/jats:italic>\n , suggesting that\n DLX5\/6<\/jats:italic>\n are activated during metastasis formation, and that their expression is alternative to that of\n DLX2<\/jats:italic>\n . The\n in vitro<\/jats:italic>\n treatment of MDA-MB-231 cells with ET1, resulted in switch from\n DLX2<\/jats:italic>\n to\n DLX5<\/jats:italic>\n expression. By data mining in microarray datasets we found that expression of\n DLX2<\/jats:italic>\n occurred in 21.6% of patients, and was significantly correlated with prolonged disease-free survival and reduced incidence of relapse. Instead,\n DLX5<\/jats:italic>\n was expressed in a small subset of cases, 2.2% of total, displaying reduced disease-free survival and high incidence of relapse which was, however, non-significantly different from the other groups due to the small size of the\n DLX+<\/jats:italic>\n cohort. In all cases, we found mutually exclusive expression of\n DLX2<\/jats:italic>\n and\n DLX5<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our studies indicate that\n DLX<\/jats:italic>\n genes are involved in human breast cancer progression, and that\n DLX2<\/jats:italic>\n and\n DLX5<\/jats:italic>\n genes might serve as prognostic markers.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/1471-2407-10-649","type":"journal-article","created":{"date-parts":[[2010,11,25]],"date-time":"2010-11-25T14:16:09Z","timestamp":1290694569000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Mutually exclusive expression of DLX2 and DLX5\/6 is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231"],"prefix":"10.1186","volume":"10","author":[{"given":"Monica","family":"Morini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Astigiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yorick","family":"Gitton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Emionite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Mirisola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Levi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavia","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,11,25]]},"reference":[{"key":"2448_CR1","doi-asserted-by":"publisher","first-page":"6766","DOI":"10.1038\/sj.onc.1210760","volume":"26","author":"B Argiropoulos","year":"2007","unstructured":"Argiropoulos B, Humphries RK: Hox genes in hematopoiesis and leukemogenesis. 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