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Expression of tripartite motif-containing protein 28 in primary breast carcinoma predicts metastasis and is involved in the stemness, chemoresistance, and tumor growth
| Content Provider | SAGE Publishing |
|---|---|
| Author | Damineni, Surekha Balaji, Sai A. Shettar, Abhijith Nayanala, Swetha Kumar, Neeraj Kruthika, Banavathy S. Subramanian, Kalyanasundaram Vijayakumar, M. Mukherjee, Geetashree Gupta, Vaijayanti Kondaiah, Paturu |
| Copyright Year | 2017 |
| Abstract | The prediction of who develops metastasis has been the most difficult aspect in the management of breast cancer patients. The lymph node metastasis has been the most useful predictor of prognosis and patient management. However, a good proportion of patients with lymph node positivity remain disease free for 5 years or more, while about a third of those who were lymph node negative develop distant metastasis within the same period. This warrants a robust biomarker(s), preferably gene expression based. In order to elucidate gene-based biomarkers for prognosis of breast cancers, gene expression profiling of primary tumors and follow-up for over 5 years has been performed. The analysis revealed a network of genes centered around the tripartite motif-containing protein 28 as an important indicator of disease progression. Short hairpin RNA–mediated knockdown of tripartite motif-containing protein 28 in breast cancer cells revealed a decreased expression of epithelial-to-mesenchymal transition markers and increased expression of epithelial markers, decreased migration and invasion, and increased chemosensitivity to doxorubicin, 5-fluorouracil, and methotrexate. Furthermore, knockdown of tripartite motif-containing protein 28 resulted in the decrease of stemness as revealed by sphere formation assay as well as decreased expression of CD44 and Bmi1. Moreover, tripartite motif-containing protein 28 knockdown significantly reduced the tumor size and lung metastasis in orthotopic tumor xenograft assay in immunocompromised mice. The tumor size was further reduced when these mice were treated with doxorubicin. These data provide evidence for tripartite motif-containing protein 28 as a biomarker and a potential therapeutic target for breast cancer. |
| Related Links | https://journals.sagepub.com/doi/pdf/10.1177/1010428317695919?download=true |
| ISSN | 10104283 |
| Issue Number | 4 |
| Volume Number | 39 |
| Journal | Tumor Biology (TUB) |
| e-ISSN | 14230380 |
| DOI | 10.1177/1010428317695919 |
| Language | English |
| Publisher | Sage Publications UK |
| Publisher Date | 2017-04-05 |
| Publisher Place | London |
| Access Restriction | Open |
| Rights Holder | © The Author(s) 2017 |
| Subject Keyword | epithelial-to-mesenchymal transition microarray stemness Tripartite motif-containing protein 28 chemoresistance |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cancer Research |