Connexin43 pseudogene in breast cancer cells offers a novel therapeutic target
| Autor: | Irene Oviedo-Landaverde, Gerald Batist, Andrew Bier, Mustapha Kandouz, Yael Mamane, Jing Zhao |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Paclitaxel Cell Survival Pseudogene Blotting Western Breast Neoplasms Biology Transfection Breast cancer Cell Line Tumor Gene expression medicine Humans Cytotoxic T cell RNA Messenger RNA Small Interfering Gene Gene knockdown Antibiotics Antineoplastic Reverse Transcriptase Polymerase Chain Reaction Cancer Suicide gene medicine.disease Antineoplastic Agents Phytogenic Molecular biology Oncology Doxorubicin Connexin 43 Polyribosomes cardiovascular system Cancer research Female sense organs biological phenomena cell phenomena and immunity Pseudogenes |
| Zdroj: | Molecular Cancer Therapeutics. 8:786-793 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.mct-08-0930 |
| Popis: | Connexin43 (Cx43) is often deregulated in breast cancer tissue compared with normal adjacent tissue. Stable reexpression of Cx43 in cancer slows growth and renders the cells more sensitive to cytotoxic chemotherapeutics. Pseudogenes are often considered nonfunctional copies of DNA. The Cx43 pseudogene (ΨCx43) possesses all the features of an expressed gene and is exclusively transcribed in breast cancer cell lines and not in normal cells. ΨCx43 can be translated in vivo, and its protein exhibits growth-suppressive behavior similar to Cx43. We showed that ΨCx43 binds to the polyribosomes in breast cancer cells and that exogenous expression of ΨCx43 induces translational inhibition of Cx43. Furthermore, ΨCx43 is translated and binds more efficiently to the translational machinery than does Cx43 in an in vitro system. Following knockdown of ΨCx43 in breast cancer cells, we observed an increase in Cx43 RNA and protein. This results in increased cellular sensitivity to cytotoxic chemotherapy. Our results show that ΨCx43 acts as a posttranscriptional regulator of Cx43 in breast cancer cells, and that this represents an example of the regulation of genes by pseudogenes with potential therapeutic implications in cancer. [Mol Cancer Ther 2009;8(4):786–93] |
| Databáze: | OpenAIRE |
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