1993 Fiscal Year Final Research Report Summary
Accumulation of alphaB-crystallin in glioma cells and the relation to oncogene expression.
| Project/Area Number |
04670213
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
IWAKI Toru Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (40221098)
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| Project Period (FY) |
1992 – 1993
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| Keywords | alphaB-ctystallin / heat shock protein / brain tumor / glioma / regulation of expression / oncogene |
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| Research Abstract |
We have identified a major component of Rosenthal fibers as alphaB-crystallin, a major lens protein. The amount of alphaB-crystallin normally present in the brain is small, but it accumulates in reactive and neoplastic glial cells and in some neurons in a variety of pathologic conditions. Thus, the accumulation of alphaB-crystallin appears to be a part of a reactive process and is required for the formation of Rosenthal fibers. To understand the significance of the accumulation of alphaB-crystallin in Rosenthal fibers within astrocytes, the expression and metabolism of alphaB-crystallin in glioma cell lines were examined under the condition of heat and oxidative stress. alphaB-crystallin mRNA was increased after both stresses and alphaB-crystallin protein moved from a detergent-soluble to a detergent-insoluble form. Next we investigated the phenotypic effects of selectively altering the levels of alphaB-crystallin in cultured glial cells by genetic manipulation. Rat C6 glioma cells and human U-373MG glioma cells were transfected with a rat alphaB-crystallin sense cDNA or an antisense cDNA to alter cellular levels of alphaB-crystallin. The anti-sense strategy resulted in decreased alphaB-crystallin levels, as revealed by Western blot and immunocytochemical analyzes. The reduced alphaB-crystallin expression was accompanied by alterations in cellular phenotype : (1)a reduction of cell size and/or a slender cell morphology ; (2)a disorganized microfilament network ; and (3)a reduction of cell adhensiveness. Like HSP27, the presence of additional alphaB-crystallin protein confers a thermoresistant phenotype to stable tranfectants. Thus, alphaB-crystallin in glioma cells plays a role in their thermal resistance and may contribute to the stability of cytoskeletal organization.
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