2010 Fiscal Year Final Research Report
Functional role of haptoglobin-β chain defined by RM2 in prostate cancer cells
| Project/Area Number |
20591849
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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 |
Urology
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
SAITO Seiichi University of the Ryukyus, 医学研究科, 教授 (80235043)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Akihiro 東北大学, 病院, 講師 (70344661)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 前立腺癌 / ハプトグロビンベータ鎖 / RM2 |
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| Research Abstract |
We have demonstrated that reactivity of prostate cancer cells to monoclonal antibody RM2 reflected the malignant potential of prostate cancer cells and haptoglobin-beta chain in prostate cancer cells carries the reactivity to RM2. In this project, we aimed to elucidate the functional roles of haptoglobin-beta chain defined by RM2.
In the prostate cancer cell lines treated with monoclonal antibody RM2, decrease of anchorage-dependent and -independent proliferation, increased apoptosis and decreased motility and invasive capacity were observed. In the prostate cancer cell lines treated with 5-Aza or PBA, decreased expression of haptoglobin-beta chain defined by RM2 and changes of expression level of signal transduction molecules toward decreased malignant phenotype. These results indicate that haptoglobin-beta chain defined by RM2 is involved in the malignant phenotype by interaction with the signal transduction molecules. It was demonstrated that many signaling pathways such as Ras-Akt, Src-FAK etc. were affected by haptoglobin-beta chain defined by RM2.
From the results described above, it was assumed that haptoglobin-beta chain defined by RM2 might affect the upper level of signaling transduction. Changes in expression level of Ras and STAT3 suggest that EGFR is a candidate molecule. After immunoprecipitation of lystates of prostate cancer cells with RM2, the bands were detected by anti-EGFR antibody in all three lines, i.e., LNCaP, PC3 and DU145. Further, treatment of cancer cells with RM2 induced intracytoplasmic movement of EGFR. These results indicate that haptoglobin-beta chain defined by RM2 stimulated Ras-Akt pathway and increased expression level of STAT3 through interaction with EGFR, leading to induction of the malignant phenotype, whereas interaction of haptoglobin-beta chain defined by RM2 with EGFR was blocked by monoclonal antibody RM2.
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