1995 Fiscal Year Final Research Report Summary
Study of the autocrine growth inhibitors of the keratinocytes
| Project/Area Number |
05670187
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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 | Tohoku University |
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Principal Investigator |
NOSE Masato Tohoku Univ. Sch. Med., pathol., Associate Prof., 医学部, 助教授 (70030913)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Mitsuyasu The Cancer Institute, Jpn Foundation for Cancer Res., Biochem., Research Fellow, 癌研究所生化学部, 研究員 (20194855)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Growth Inhibitor / Autocrine / Keratinocytes / Histogenesis / Cancer |
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| Research Abstract |
1.Identification of autocrine growth inhibitors of keratinocytes : We identified transforming growth factor-beta (TGF-beta) and activin as autocrine growth inhibitors of the keratinocytes. Additionally, two more growth inhibitors were purified from the culture media conditioned by confluent keratinocytes. One of them was recognized to be insulin-like growth factor binding protein-6 (IGFBP-6). Indentification of the other molecule is still going on.
2.Tissue distribution : Among three isoforms of TGF-betas, only TGF-beta2 was detected in epidermal tissue of normal human skin. Activin and IGFBP-6 were also found in human epidermis, and all of these ligands distributed in whole cellular layrs of epidermis. On the other hand, type I and type II receptors for TGF-beta, and type IB and type II receptors for activin were expressed on a spinous layr of the epidermis where keratinocytes were differentiating.
3.Abnormality of the autocrine growth inhibitor systems in cancer cells : All of 15 examined squamous cell carcinoma cell lines had abolished or reduced responsiveness to TGF-beta. Among these, however, most cell lines expressed enhanced amounts of TGF-beta receptors, and only two of them did not have detectable level of TGF-beta receptors. These results were different from replication error positive cases of colo-rectal cancer of hereditary non-polypotic colon cancer patients, in which more than 90% cases of cancer cells have mutation on the gene of TGF-beta type II receptor, and lost the receptor expression. We also studied the abnormality of the receptors in gastric cancer, prostatic cancer, glioblastoma and T cell leukemia. Most of these cancers also had reduced responsiveness to TGF-beta but molecular abnormality causing the phenomena seemed diverse.
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Research Products
(12 results)
