The Journal of biological chemistry, 2010-11, Vol.285 (47), p.36842-36848
2010
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- Autor(en) / Beteiligte
- Titel
- CXCR3-B Can Mediate Growth-inhibitory Signals in Human Renal Cancer Cells by Down-regulating the Expression of Heme Oxygenase-1
- Ist Teil von
- The Journal of biological chemistry, 2010-11, Vol.285 (47), p.36842-36848
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The chemokine receptor CXCR3 may play a critical role in the growth and metastasis of tumor cells, including renal tumors. It has been shown that CXCR3 has two splice variants with completely opposite functions; CXCR3-A promotes cell proliferation, whereas CXCR3-B inhibits cell growth. We recently demonstrated that the expression of growth-promoting CXCR3-A is up-regulated, and the growth-inhibitory CXCR3-B is markedly down-regulated in human renal cancer tissues; and the overexpression of CXCR3-B in renal cancer cells can significantly inhibit cell proliferation. However, the growth-inhibitory signal(s) through CXCR3-B are not well characterized. Here, we investigated the effector molecule(s) involved in CXCR3-B-mediated signaling events. We found that the overexpression of CXCR3-B in human renal cancer cells (Caki-1) promoted cellular apoptosis as observed by FACS analysis through Annexin-V staining. To examine whether the overexpression of CXCR3-B could alter the expression of any apoptosis-related genes in renal cancer cells, we performed a protein array. We found that CXCR3-B overexpression significantly down-regulated the expression of antiapoptotic heme oxygenase-1 (HO-1). By utilizing a HO-1 promoter-luciferase plasmid, we showed that CXCR3-B-mediated down-regulation of HO-1 was controlled at the transcriptional level as observed by luciferase assay. We also demonstrated that the inhibition of HO-1 expression using siRNA promoted apoptosis of renal cancer cells. Finally, we observed that human renal cancer tissues expressing low amounts of CXCR3-B significantly overexpress HO-1 at both mRNA and protein level. Together, we suggest that the overexpression of CXCR3-B may prevent the growth of renal tumors through the inhibition of antiapoptotic HO-1.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9258eISSN: 1083-351XDOI: 10.1074/jbc.M110.170324Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2978613
- Format
- –
- Schlagworte
- Apoptosis, Blotting, Western, Cancer Tumor Promoter, Carcinoma, Renal Cell - genetics, Carcinoma, Renal Cell - metabolism, Carcinoma, Renal Cell - pathology, Chemokines, Down-Regulation, Flow Cytometry, Gene Regulation, Growth Inhibitors - genetics, Growth Inhibitors - metabolism, Heme, Heme Oxygenase-1 - antagonists & inhibitors, Heme Oxygenase-1 - genetics, Heme Oxygenase-1 - metabolism, HO-1, Humans, Immunoenzyme Techniques, Kidney, Kidney Neoplasms - genetics, Kidney Neoplasms - metabolism, Kidney Neoplasms - pathology, Luciferases - metabolism, Receptors, CXCR3 - genetics, Receptors, CXCR3 - metabolism, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger - genetics, RNA, Small Interfering - genetics, Signal Transduction, Tumor Cells, Cultured