1995 Fiscal Year Final Research Report Summary
Molecular biological study on the significance of keratinocyte-substratum interaction for their existence and proliferation-comparison with cancer cells-
| Project/Area Number |
06807071
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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 |
Dermatology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
KATAYAMA Hiroshi Jichi Medical School, Dermatology, Lecturer, 医学部, 講師 (50142401)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Cell-Substratum interaction / Anchorage-dependency / Detachment / Keratinocyte / Squamous cell carcinoma cell / Focal adhesion kinase / Tyrosine phosphorylation / Laminin |
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| Research Abstract |
Normal cells in culture other than blood cells can not grow without attachment to the substratum. This is a phenomenon called anchorage-dependency. Several malignant cells are known to be anchorage-independent. Focal adhesion kinase (FAK) is a recently described non-receptor type protein-tyrosine kinase that localizes at cell-substratum attachment sites named focal adhesion. FAK is supposed to be activated, possibly by tyrosine autophosphorylation, when cells attach to extracellular matrix and transmit signals for growth and differentiation. In this study we examined FAK expression and its tyrosine phosphorylation in both attached and detached forms of cultured normal human keratinocytes and their malignant counterpart, human epidermal carcinoma cell line (DJM-1), in order to clarify how cell-substratum interaction and FAK are involved in their survival and growth. DJM-1 kept detached and dissociated by elastase survived at least 3 weeks. Survived cells (approximately 30% of the total)
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rapidly proliferated when released from detachment. Their FAK assayd at one week in detachment was tyrosine-phosphorylated in a degree slightly decreased than that when they were attached to wells. Majority of keratinocytes kept detached by elastase disappeared within a week. They lost the ability to proliferate when kept detached only for 3 days. FAK in keratinocytes detached by addition of elastase for 24h was hardly tyrosine-phosphorylated. These facts suggested a close association of sustained FAK tyrosine phosphorylation with their prolonged survival in detached DJM-1. Detached DJM-1 expressed laminin on their surfaces as well as integrins alpha_2beta_1, alpha_3beta_1 and alpha_6beta_4, all of which mediate keratinocyte adhesion to laminin. Thus their interactions on cell membrane might have playd a role in FAK tyrosine phosphorylation in detached DJM-1. Curiously, detached DJM-1 had fungus-like appearance. Results obtained in this study could greatly contribute to human efforts to eradicate cancers. Less
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