TGF-beta 1 and skin carcinogenesis: antiproliferative effect in vitro and TGF-beta 1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis
The role of transforming growth factor-beta 1 (TGF-beta 1) in multisage carcinogenesis in mouse skin was assessed by studying its growth inhibitory effects on nontumorigenic and tumorigenic keratinocytes and by examining its mRNA expression in vitro and during epidermal hyperproliferation and multis...
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| Veröffentlicht in: | Molecular carcinogenesis 1991, Vol.4 (2), p.129 |
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| creator | Krieg, P Schnapke, R Fürstenberger, G Vogt, I Marks, F |
| description | The role of transforming growth factor-beta 1 (TGF-beta 1) in multisage carcinogenesis in mouse skin was assessed by studying its growth inhibitory effects on nontumorigenic and tumorigenic keratinocytes and by examining its mRNA expression in vitro and during epidermal hyperproliferation and multistage carcinogenesis. While growth of primary basal keratinocytes was inhibited by TGF-beta 1 in doses as low as 0.1 ng/mL, the immortal keratinocyte line MCA/3D ("putatively initiated" cells) responded to TGF-beta 1 with slightly reduced sensitivity, and the papilloma-producing keratinocyte line 308 was considerably less sensitive. In contrast, the squamous carcinoma cell line Carc B was completely nonresponsive, and two other tumorigenic cell lines (PDV and PDVC57) were sensitive to growth inhibition by TGF-beta 1. Steady-state levels of TGF-beta 1 mRNA were high in all the malignant cell lines and in line 308 papilloma cells, but low in primary basal cells and in the nontumorigenic keratinocyte lines V2, Reb1, and MCA/3D. Our in vivo studies showed that tumor promoters, but not mitogenic or weak hyperplasiogenic agents, were able to induce transient expression of TGF-beta 1 mRNA in mouse epidermis. A constitutive overexpression of TGF-beta 1 mRNA was observed in malignant carcinomas but not in the benign premalignant lesions, indicating that overexpression may be associated with malignant progression. |
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While growth of primary basal keratinocytes was inhibited by TGF-beta 1 in doses as low as 0.1 ng/mL, the immortal keratinocyte line MCA/3D ("putatively initiated" cells) responded to TGF-beta 1 with slightly reduced sensitivity, and the papilloma-producing keratinocyte line 308 was considerably less sensitive. In contrast, the squamous carcinoma cell line Carc B was completely nonresponsive, and two other tumorigenic cell lines (PDV and PDVC57) were sensitive to growth inhibition by TGF-beta 1. Steady-state levels of TGF-beta 1 mRNA were high in all the malignant cell lines and in line 308 papilloma cells, but low in primary basal cells and in the nontumorigenic keratinocyte lines V2, Reb1, and MCA/3D. Our in vivo studies showed that tumor promoters, but not mitogenic or weak hyperplasiogenic agents, were able to induce transient expression of TGF-beta 1 mRNA in mouse epidermis. A constitutive overexpression of TGF-beta 1 mRNA was observed in malignant carcinomas but not in the benign premalignant lesions, indicating that overexpression may be associated with malignant progression.</description><identifier>ISSN: 0899-1987</identifier><identifier>PMID: 1710462</identifier><language>eng</language><publisher>United States</publisher><subject>9,10-Dimethyl-1,2-benzanthracene - toxicity ; Animals ; Animals, Newborn ; Blotting, Northern ; Cell Division - drug effects ; Cell Transformation, Neoplastic ; Cells, Cultured ; DNA - genetics ; DNA - isolation & purification ; DNA Replication - drug effects ; DNA, Neoplasm - genetics ; DNA, Neoplasm - isolation & purification ; Female ; Gene Expression ; Keratinocytes - cytology ; Keratinocytes - drug effects ; Mice ; Mice, Inbred Strains ; Phorbol Esters - toxicity ; RNA - genetics ; RNA - isolation & purification ; RNA, Messenger - genetics ; RNA, Neoplasm - genetics ; RNA, Neoplasm - isolation & purification ; Skin - drug effects ; Skin - pathology ; Skin Neoplasms - chemically induced ; Skin Neoplasms - genetics ; Skin Neoplasms - pathology ; Skin Physiological Phenomena ; Tetradecanoylphorbol Acetate - toxicity ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - pharmacology</subject><ispartof>Molecular carcinogenesis, 1991, Vol.4 (2), p.129</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,4012</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1710462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krieg, P</creatorcontrib><creatorcontrib>Schnapke, R</creatorcontrib><creatorcontrib>Fürstenberger, G</creatorcontrib><creatorcontrib>Vogt, I</creatorcontrib><creatorcontrib>Marks, F</creatorcontrib><title>TGF-beta 1 and skin carcinogenesis: antiproliferative effect in vitro and TGF-beta 1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis</title><title>Molecular carcinogenesis</title><addtitle>Mol Carcinog</addtitle><description>The role of transforming growth factor-beta 1 (TGF-beta 1) in multisage carcinogenesis in mouse skin was assessed by studying its growth inhibitory effects on nontumorigenic and tumorigenic keratinocytes and by examining its mRNA expression in vitro and during epidermal hyperproliferation and multistage carcinogenesis. While growth of primary basal keratinocytes was inhibited by TGF-beta 1 in doses as low as 0.1 ng/mL, the immortal keratinocyte line MCA/3D ("putatively initiated" cells) responded to TGF-beta 1 with slightly reduced sensitivity, and the papilloma-producing keratinocyte line 308 was considerably less sensitive. In contrast, the squamous carcinoma cell line Carc B was completely nonresponsive, and two other tumorigenic cell lines (PDV and PDVC57) were sensitive to growth inhibition by TGF-beta 1. Steady-state levels of TGF-beta 1 mRNA were high in all the malignant cell lines and in line 308 papilloma cells, but low in primary basal cells and in the nontumorigenic keratinocyte lines V2, Reb1, and MCA/3D. Our in vivo studies showed that tumor promoters, but not mitogenic or weak hyperplasiogenic agents, were able to induce transient expression of TGF-beta 1 mRNA in mouse epidermis. A constitutive overexpression of TGF-beta 1 mRNA was observed in malignant carcinomas but not in the benign premalignant lesions, indicating that overexpression may be associated with malignant progression.</description><subject>9,10-Dimethyl-1,2-benzanthracene - toxicity</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Blotting, Northern</subject><subject>Cell Division - drug effects</subject><subject>Cell Transformation, Neoplastic</subject><subject>Cells, Cultured</subject><subject>DNA - genetics</subject><subject>DNA - isolation & purification</subject><subject>DNA Replication - drug effects</subject><subject>DNA, Neoplasm - genetics</subject><subject>DNA, Neoplasm - isolation & purification</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Keratinocytes - cytology</subject><subject>Keratinocytes - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Phorbol Esters - toxicity</subject><subject>RNA - genetics</subject><subject>RNA - isolation & purification</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Neoplasm - genetics</subject><subject>RNA, Neoplasm - isolation & purification</subject><subject>Skin - drug effects</subject><subject>Skin - pathology</subject><subject>Skin Neoplasms - chemically induced</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - pathology</subject><subject>Skin Physiological Phenomena</subject><subject>Tetradecanoylphorbol Acetate - toxicity</subject><subject>Transforming Growth Factor beta - genetics</subject><subject>Transforming Growth Factor beta - pharmacology</subject><issn>0899-1987</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1OwzAUhL0AlVI4ApIvEMnOS-OEXVXRglSBhLqvHPulPMiPZTsVPRD3JJQuuprFzHwazRWbiqIsE1kW6obdhvAphJRqLiZsIpUUWZ5O2c92vUoqjJpLrjvLwxd13GhvqOv32GGg8DgakZzvG6rR60gH5FjXaCIfsweKvj9VL0jt--uC47fzGAL1HbeDp27P0ZFF3-qGfxwd-gvkmPlDtEMTKUS9Rx6Htvd0nnDHrmvdBLw_64xtV0_b5XOyeVu_LBebxM0hTWxdKlGCFlll8hQhFwqMEgCQaVFBCtKmc8hNBjkqCQWUolDV-IhJC23zGmbs4R_rhqpFu3OeWu2Pu_Nb8AtAWWel</recordid><startdate>1991</startdate><enddate>1991</enddate><creator>Krieg, P</creator><creator>Schnapke, R</creator><creator>Fürstenberger, G</creator><creator>Vogt, I</creator><creator>Marks, F</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>1991</creationdate><title>TGF-beta 1 and skin carcinogenesis: antiproliferative effect in vitro and TGF-beta 1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis</title><author>Krieg, P ; Schnapke, R ; Fürstenberger, G ; Vogt, I ; Marks, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p532-df97093a04bc62e36073c703334a0b3231d2536c436e713839087b175c28ad6f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>9,10-Dimethyl-1,2-benzanthracene - toxicity</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Blotting, Northern</topic><topic>Cell Division - drug effects</topic><topic>Cell Transformation, Neoplastic</topic><topic>Cells, Cultured</topic><topic>DNA - genetics</topic><topic>DNA - isolation & purification</topic><topic>DNA Replication - drug effects</topic><topic>DNA, Neoplasm - genetics</topic><topic>DNA, Neoplasm - isolation & purification</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Keratinocytes - cytology</topic><topic>Keratinocytes - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Phorbol Esters - toxicity</topic><topic>RNA - genetics</topic><topic>RNA - isolation & purification</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Neoplasm - genetics</topic><topic>RNA, Neoplasm - isolation & purification</topic><topic>Skin - drug effects</topic><topic>Skin - pathology</topic><topic>Skin Neoplasms - chemically induced</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - pathology</topic><topic>Skin Physiological Phenomena</topic><topic>Tetradecanoylphorbol Acetate - toxicity</topic><topic>Transforming Growth Factor beta - genetics</topic><topic>Transforming Growth Factor beta - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krieg, P</creatorcontrib><creatorcontrib>Schnapke, R</creatorcontrib><creatorcontrib>Fürstenberger, G</creatorcontrib><creatorcontrib>Vogt, I</creatorcontrib><creatorcontrib>Marks, F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Molecular carcinogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krieg, P</au><au>Schnapke, R</au><au>Fürstenberger, G</au><au>Vogt, I</au><au>Marks, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TGF-beta 1 and skin carcinogenesis: antiproliferative effect in vitro and TGF-beta 1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis</atitle><jtitle>Molecular carcinogenesis</jtitle><addtitle>Mol Carcinog</addtitle><date>1991</date><risdate>1991</risdate><volume>4</volume><issue>2</issue><spage>129</spage><pages>129-</pages><issn>0899-1987</issn><abstract>The role of transforming growth factor-beta 1 (TGF-beta 1) in multisage carcinogenesis in mouse skin was assessed by studying its growth inhibitory effects on nontumorigenic and tumorigenic keratinocytes and by examining its mRNA expression in vitro and during epidermal hyperproliferation and multistage carcinogenesis. While growth of primary basal keratinocytes was inhibited by TGF-beta 1 in doses as low as 0.1 ng/mL, the immortal keratinocyte line MCA/3D ("putatively initiated" cells) responded to TGF-beta 1 with slightly reduced sensitivity, and the papilloma-producing keratinocyte line 308 was considerably less sensitive. In contrast, the squamous carcinoma cell line Carc B was completely nonresponsive, and two other tumorigenic cell lines (PDV and PDVC57) were sensitive to growth inhibition by TGF-beta 1. Steady-state levels of TGF-beta 1 mRNA were high in all the malignant cell lines and in line 308 papilloma cells, but low in primary basal cells and in the nontumorigenic keratinocyte lines V2, Reb1, and MCA/3D. Our in vivo studies showed that tumor promoters, but not mitogenic or weak hyperplasiogenic agents, were able to induce transient expression of TGF-beta 1 mRNA in mouse epidermis. A constitutive overexpression of TGF-beta 1 mRNA was observed in malignant carcinomas but not in the benign premalignant lesions, indicating that overexpression may be associated with malignant progression.</abstract><cop>United States</cop><pmid>1710462</pmid></addata></record> |
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| identifier | ISSN: 0899-1987 |
| ispartof | Molecular carcinogenesis, 1991, Vol.4 (2), p.129 |
| issn | 0899-1987 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | 9,10-Dimethyl-1,2-benzanthracene - toxicity Animals Animals, Newborn Blotting, Northern Cell Division - drug effects Cell Transformation, Neoplastic Cells, Cultured DNA - genetics DNA - isolation & purification DNA Replication - drug effects DNA, Neoplasm - genetics DNA, Neoplasm - isolation & purification Female Gene Expression Keratinocytes - cytology Keratinocytes - drug effects Mice Mice, Inbred Strains Phorbol Esters - toxicity RNA - genetics RNA - isolation & purification RNA, Messenger - genetics RNA, Neoplasm - genetics RNA, Neoplasm - isolation & purification Skin - drug effects Skin - pathology Skin Neoplasms - chemically induced Skin Neoplasms - genetics Skin Neoplasms - pathology Skin Physiological Phenomena Tetradecanoylphorbol Acetate - toxicity Transforming Growth Factor beta - genetics Transforming Growth Factor beta - pharmacology |
| title | TGF-beta 1 and skin carcinogenesis: antiproliferative effect in vitro and TGF-beta 1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis |
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