XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth
| Autor: | Sylvia L. Asa, Shaf Keshavjee, Jeya Nadesalingam, Atsushi Shiozaki, Xiao-Hui Bai, Daniel A. Winer, Monika Lodyga, Mingyao Liu, Takeshi Oyaizu |
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| Rok vydání: | 2011 |
| Předmět: |
Cell Survival
Mice Nude Biology Transfection medicine.disease_cause Pathology and Forensic Medicine Small hairpin RNA Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Humans Thyroid Neoplasms RNA Small Interfering Thyroid cancer Adaptor Proteins Signal Transducing Cell Proliferation 030304 developmental biology XB130 0303 health sciences Cell growth Gene Expression Profiling Carcinoma Cell Cycle Signal transducing adaptor protein Regular Article Cell cycle medicine.disease 3. Good health Cell biology Tissue Array Analysis 030220 oncology & carcinogenesis Cancer cell Carcinogenesis |
| Zdroj: | The American Journal of Pathology. 178:391-401 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2010.11.024 |
| Popis: | Adaptor proteins with multimodular structures can participate in the regulation of various cellular functions. We have cloned a novel adaptor protein, XB130, which binds the p85α subunit of phosphatidyl inositol 3-kinase and subsequently mediates signaling through RET/PTC in TPC-1 thyroid cancer cells. In the present study, we sought to determine the role of XB130 in the tumorigenesis in vivo and in related molecular mechanisms. In WRO thyroid cancer cells, knockdown of XB130 using small interfering RNA inhibited G 1 -S phase progression, induced spontaneous apoptosis, and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Growth of tumors in nude mice formed from XB130 shRNA stably transfected WRO cells were significantly reduced, with decreased cell proliferation and increased apoptosis. Microarray analysis identified 246 genes significantly changed in XB130 shRNA transfected cells. Among them, 57 genes are related to cell proliferation or survival, including many transcription regulators. Ingenuity Pathway Analysis showed that the top-ranked disease related to XB130 is cancer, and the top molecular and cellular functions are cellular growth and proliferation and cell cycle. A human thyroid tissue microarray study identified expression of XB130 in normal thyroid tissue as well as in human thyroid carcinomas. These observations suggest that the expression of XB130 in these cancer cells may affect cell proliferation and survival by controlling the expression of multiple genes, especially transcription regulators. |
| Databáze: | OpenAIRE |
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