| Project/Area Number |
18590342
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
IMURA Johji Dokkyo Medical University, Pathology, Associate Professor (80316554)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,520,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | cancer / Pathology / gene / clinic / metastasis |
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| Research Abstract |
We examined the expression of CXCR4 at the invasive front of human esophageal cancer (EC) tissues by immunohistochemistry and found that its signal is localized not only in the cytoplasm and cell membrane but also in the nucleus of EC cells. Supporting this finding, we confirmed that CXCR4 is expressed in both protein fractions of separately isolated cyto-membrane and nuclei from T.Tn EC cells. Moreover, we investigated the relationship between the immunostaining pattern of CXCR4 and clinicopathological features in patients with EC. Subsequently, we suggested that EC patients showing nuclear CXCR4 pattern had significantly worse prognosis.
We next examined the expression of SDF-1α (ligand for CXCR4) and phosphorylated EGF receptor (pEGFR; candidate partner for signal closstalking) in EC tissues. Interestingly, EC patients with nuclear CXCR4 pattern significantly showed strong SDF-1a and nuclear pEGFR expression. These findings suggest that SDF-la and/or EGF signaling may be involved in the nuclear expression of CXCR4 in EC cells.
To clarify the regulatory factor for nuclear CXCR4 expression in EC cells, we cultured T.Tn EC cells under hypoxic condition. Hypoxia stimulation enhanced membrane CXCR4 expression but reduced the nuclear ones in T.Tn EC cells. In the future studies, we will clarify whether the translocation of CXCR4 expression in T.Tn EC cells may be associated with the change of biology such as invasion or migration.
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