Mutually exclusive expression of <it>DLX2 </it>and <it>DLX5/6 </it>is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231
<p>Abstract</p> <p>Background</p> <p>The <it>DLX </it>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 br...
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| Format: | Article |
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BMC
2010-11-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/649 |
| _version_ | 1818689036973244416 |
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| author | Mirisola Valentina Emionite Laura Gitton Yorick Astigiano Simonetta Morini Monica Levi Giovanni Barbieri Ottavia |
| author_facet | Mirisola Valentina Emionite Laura Gitton Yorick Astigiano Simonetta Morini Monica Levi Giovanni Barbieri Ottavia |
| author_sort | Mirisola Valentina |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The <it>DLX </it>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 <it>DLX </it>gene expression was found in human solid tumors and hematologic malignancies. In particular, <it>DLX4 </it>overexpression represents a possible prognostic marker in ovarian cancer. We have investigated the role of <it>DLX </it>genes in human breast cancer progression.</p> <p>Methods</p> <p>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 <it>DLX2</it>, <it>DLX5 </it>and <it>DLX6 </it>was assessed in cultured cells, either treated or not with ET1, tumors and metastases by RT-PCR. <it>In situ </it>hybridization was used to confirm <it>DLX </it>gene expression in primary tumors and in lung and bone metastases. The expression of <it>DLX2 </it>and <it>DLX5 </it>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 <it>DLX2</it>/<it>DLX5 </it>expression.</p> <p>Results</p> <p>Before injection, or after subcutaneous growth, MDA-MB-231 cells expressed <it>DLX2 </it>but neither <it>DLX5 </it>nor <it>DLX6</it>. Instead, in bone and lung metastases resulting from intravenous injection we detected expression of <it>DLX5/6 </it>but not of <it>DLX2</it>, suggesting that <it>DLX5/6 </it>are activated during metastasis formation, and that their expression is alternative to that of <it>DLX2</it>. The <it>in vitro </it>treatment of MDA-MB-231 cells with ET1, resulted in switch from <it>DLX2 </it>to <it>DLX5 </it>expression. By data mining in microarray datasets we found that expression of <it>DLX2 </it>occurred in 21.6% of patients, and was significantly correlated with prolonged disease-free survival and reduced incidence of relapse. Instead, <it>DLX5 </it>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 <it>DLX+ </it>cohort. In all cases, we found mutually exclusive expression of <it>DLX2 </it>and <it>DLX5</it>.</p> <p>Conclusions</p> <p>Our studies indicate that <it>DLX </it>genes are involved in human breast cancer progression, and that <it>DLX2 </it>and <it>DLX5 </it>genes might serve as prognostic markers.</p> |
| first_indexed | 2024-12-17T12:03:44Z |
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| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-17T12:03:44Z |
| publishDate | 2010-11-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-deba2d881ec6459fa5c616953b8b51f22022-12-21T21:49:43ZengBMCBMC Cancer1471-24072010-11-0110164910.1186/1471-2407-10-649Mutually exclusive expression of <it>DLX2 </it>and <it>DLX5/6 </it>is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231Mirisola ValentinaEmionite LauraGitton YorickAstigiano SimonettaMorini MonicaLevi GiovanniBarbieri Ottavia<p>Abstract</p> <p>Background</p> <p>The <it>DLX </it>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 <it>DLX </it>gene expression was found in human solid tumors and hematologic malignancies. In particular, <it>DLX4 </it>overexpression represents a possible prognostic marker in ovarian cancer. We have investigated the role of <it>DLX </it>genes in human breast cancer progression.</p> <p>Methods</p> <p>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 <it>DLX2</it>, <it>DLX5 </it>and <it>DLX6 </it>was assessed in cultured cells, either treated or not with ET1, tumors and metastases by RT-PCR. <it>In situ </it>hybridization was used to confirm <it>DLX </it>gene expression in primary tumors and in lung and bone metastases. The expression of <it>DLX2 </it>and <it>DLX5 </it>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 <it>DLX2</it>/<it>DLX5 </it>expression.</p> <p>Results</p> <p>Before injection, or after subcutaneous growth, MDA-MB-231 cells expressed <it>DLX2 </it>but neither <it>DLX5 </it>nor <it>DLX6</it>. Instead, in bone and lung metastases resulting from intravenous injection we detected expression of <it>DLX5/6 </it>but not of <it>DLX2</it>, suggesting that <it>DLX5/6 </it>are activated during metastasis formation, and that their expression is alternative to that of <it>DLX2</it>. The <it>in vitro </it>treatment of MDA-MB-231 cells with ET1, resulted in switch from <it>DLX2 </it>to <it>DLX5 </it>expression. By data mining in microarray datasets we found that expression of <it>DLX2 </it>occurred in 21.6% of patients, and was significantly correlated with prolonged disease-free survival and reduced incidence of relapse. Instead, <it>DLX5 </it>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 <it>DLX+ </it>cohort. In all cases, we found mutually exclusive expression of <it>DLX2 </it>and <it>DLX5</it>.</p> <p>Conclusions</p> <p>Our studies indicate that <it>DLX </it>genes are involved in human breast cancer progression, and that <it>DLX2 </it>and <it>DLX5 </it>genes might serve as prognostic markers.</p>http://www.biomedcentral.com/1471-2407/10/649 |
| spellingShingle | Mirisola Valentina Emionite Laura Gitton Yorick Astigiano Simonetta Morini Monica Levi Giovanni Barbieri Ottavia Mutually exclusive expression of <it>DLX2 </it>and <it>DLX5/6 </it>is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231 BMC Cancer |
| title | Mutually exclusive expression of <it>DLX2 </it>and <it>DLX5/6 </it>is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231 |
| title_full | Mutually exclusive expression of <it>DLX2 </it>and <it>DLX5/6 </it>is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231 |
| title_fullStr | Mutually exclusive expression of <it>DLX2 </it>and <it>DLX5/6 </it>is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231 |
| title_full_unstemmed | Mutually exclusive expression of <it>DLX2 </it>and <it>DLX5/6 </it>is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231 |
| title_short | Mutually exclusive expression of <it>DLX2 </it>and <it>DLX5/6 </it>is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231 |
| title_sort | mutually exclusive expression of it dlx2 it and it dlx5 6 it is associated with the metastatic potential of the human breast cancer cell line mda mb 231 |
| url | http://www.biomedcentral.com/1471-2407/10/649 |
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