1988 Fiscal Year Final Research Report Summary
STUDIES ON THE DIFFERENTIATED FUNCTION AND GROWTH OF THYROID FOLLICULAR CELLS.
Project/Area Number |
62480252
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
内分泌・代謝学
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Research Institution | Kyoto University |
Principal Investigator |
MORI Toru CLINICAL MOLECULAR BIOLOGY, FACULTY OF MEDICINE, 医学部, 助教授 (40026894)
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Project Period (FY) |
1987 – 1988
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Keywords | Growth And Differentiated Functions Of Thyroid Cells / FRTL-5 / TSH / EGF / IGF-1 / TPA / IL-1alpha / EGF Receptor / Cell Fusion / Undifferentiated Thyroid Cancer Cell Line / TGF-alpha / CSF / PTH Like Substance / Thyroglobulin / 甲状腺ホルモン |
Research Abstract |
CELL GROWTH AND DIFFERENTIATED FUNCTIONS OF THE THYROID FOLLICULAR CELLS WERE STUDIED USING HUMAN AND ANIMAL THYROIDS. FUNCTIONING FISHER RAT THYROID CELLS (FRTL-5) WERE FOUND TO HAVE ABNORMALITY ON THE EGFBINDING DOMAIN, BUT THEIR POSSESSION OF EGF-RECEPTOR WAS PROVED USING SPECIFIC CDNA PROBES AND MONOCLONAL ANTIBODIES. MUTANT CLONES WITH 8-AZAGUANINE RESISTANCE WERE OBTAINED FROM THE FRTL-5 CELLS. THESE WERE APPLIED TO THE CELL-FUSION STUDY WITH SEVERAL HUMAN CELLS. RESULTS OBTAINED WERE OF VERY INTRIGUING TO SEE THE DEVELOPMENT OF DIFFERENTIATED FUNCTIONS AND THEIR GENE EXPRESSION. EFFECTS OF INTERLEUKIN-1 ALPHA ON THE MOUSE THYROID WERE STUDIED. DURING ADMINISTRATION OF IL-1 FOR 7 DAYS. THE THYROID FUNCTIONS WERE GREATLY SUPPRESSED. FURTHER. AFTER 3 WEEKS OF IL-1 ADMINISTRATION, THE THYROID ACQUIRED UNRESPONSIVENESS TO TSH AND PITUITARY TSH CONTENTS WERE INCREASED. USING PRIMARY CULTURE OF VARIOUS HUMAN THYROCYTES, PROPERTIES OF EGF RECEPTOR AND GROWTH EFFECTS OF EGF AND TSH WERE STUDIED. CANCER CELLS HAD SIGNIFICANTLY SMALLER BINDING AFFINITY BUT WELL RESPONDED TO EGF. NORMAL (NON-NEOPLASTIC) AND BENIGN TUMOR CELLS WERE FOUND TO SHOW A CLOSE NEGATIVE CORRELATION BETWEEN BINDING AFFINITY OF EGF RECEPTOR AND GROWTH STIMULATORY 3HTHYMIDINE INCORPORATION BY EXOGENOUS EGF. A CELL LINE WAS ESTABLISHED FROM TUMOR CELLS OF A PATIENT WITH UNDIFFERENTIATED GIANT CELL THYROID CANCER. THESE CELLS HAVE BEEN PRODUCING SEVERAL GROWTH FACTORS AND CYTOKINES SUCH AD TGF-ALPHA, IL-1 ALPHA, CSF AND PTH LIKE SUBSTANCE. GROWTH OF THEM IS GREATLY DEPENDENT ON SERUM COMPONENT AND IS ALSO AFFECTED BY VARIOUS GROWTH FACTORS. IN SUMMARY, QUITE A FEW NOVEL EVIDENCES CONCERNING WITH THE THYROID CELL GROWTH AND THEDIFFERENTIATED FUNCTIONS WERE OBTAINED. MOST OF THEM WILL SURELY BE USEFUL FOR THE FUTURE DEVELOPMENT OF THE RESEARCHES AND THEIR CLINICAL APPLICATIONS IN THE THYROID STUDIES.
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