Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA
Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 ( Ppp6c ) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of Ppp6c in carcinogenesis, we generated skin keratinocyte-sp...
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| creator | Hayashi, K Momoi, Y Tanuma, N Kishimoto, A Ogoh, H Kato, H Suzuki, M Sakamoto, Y Inoue, Y Nomura, M Kiyonari, H Sakayori, M Fukamachi, K Kakugawa, Y Yamashita, Y Ito, S Sato, I Suzuki, A Nishio, M Suganuma, M Watanabe, T Shima, H |
| description | Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 (
Ppp6c
) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of
Ppp6c
in carcinogenesis, we generated skin keratinocyte-specific
Ppp6c
conditional knockout mice and performed two-stage skin carcinogenesis analysis.
Ppp6c
deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1β was enhanced in
Ppp6c
-deficient keratinocytes. Overall, we conclude that
Ppp6c
deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice. |
| doi_str_mv | 10.1038/onc.2014.398 |
| format | Article |
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Ppp6c
) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of
Ppp6c
in carcinogenesis, we generated skin keratinocyte-specific
Ppp6c
conditional knockout mice and performed two-stage skin carcinogenesis analysis.
Ppp6c
deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1β was enhanced in
Ppp6c
-deficient keratinocytes. Overall, we conclude that
Ppp6c
deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2014.398</identifier><identifier>PMID: 25486434</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/95 ; 14/63 ; 45/41 ; 631/67/581 ; 64/60 ; 9,10-Dimethyl-1,2-benzanthracene ; 96/1 ; Acetic acid ; Animals ; Anthracene ; Apoptosis ; Carcinogenesis ; Carcinogenesis - metabolism ; Cell Biology ; Cells, Cultured ; Gene mutations ; Human Genetics ; Internal Medicine ; Keratinocytes ; Keratinocytes - enzymology ; Medicine ; Medicine & Public Health ; Melanoma ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Transgenic ; Mutation ; NF-kappa B - metabolism ; NF-κB protein ; Oncology ; original-article ; Papilloma ; Phosphatase ; Phosphatases ; Phosphoprotein Phosphatases - genetics ; Phosphoprotein Phosphatases - metabolism ; Protein phosphatase ; Proteins ; Raf protein ; Rodents ; Signal Transduction ; Skin ; Skin - enzymology ; Skin - pathology ; Skin cancer ; Skin Neoplasms - chemically induced ; Skin Neoplasms - enzymology ; Studies ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Tumorigenesis</subject><ispartof>Oncogene, 2015-08, Vol.34 (35), p.4647-4655</ispartof><rights>Macmillan Publishers Limited 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 27, 2015</rights><rights>Macmillan Publishers Limited 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-7ce5ef2459f98380cf44bdc3cd9bca041b87ad2eb353c542b50eb4f54402126d3</citedby><cites>FETCH-LOGICAL-c593t-7ce5ef2459f98380cf44bdc3cd9bca041b87ad2eb353c542b50eb4f54402126d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2014.398$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2014.398$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25486434$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hayashi, K</creatorcontrib><creatorcontrib>Momoi, Y</creatorcontrib><creatorcontrib>Tanuma, N</creatorcontrib><creatorcontrib>Kishimoto, A</creatorcontrib><creatorcontrib>Ogoh, H</creatorcontrib><creatorcontrib>Kato, H</creatorcontrib><creatorcontrib>Suzuki, M</creatorcontrib><creatorcontrib>Sakamoto, Y</creatorcontrib><creatorcontrib>Inoue, Y</creatorcontrib><creatorcontrib>Nomura, M</creatorcontrib><creatorcontrib>Kiyonari, H</creatorcontrib><creatorcontrib>Sakayori, M</creatorcontrib><creatorcontrib>Fukamachi, K</creatorcontrib><creatorcontrib>Kakugawa, Y</creatorcontrib><creatorcontrib>Yamashita, Y</creatorcontrib><creatorcontrib>Ito, S</creatorcontrib><creatorcontrib>Sato, I</creatorcontrib><creatorcontrib>Suzuki, A</creatorcontrib><creatorcontrib>Nishio, M</creatorcontrib><creatorcontrib>Suganuma, M</creatorcontrib><creatorcontrib>Watanabe, T</creatorcontrib><creatorcontrib>Shima, H</creatorcontrib><title>Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 (
Ppp6c
) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of
Ppp6c
in carcinogenesis, we generated skin keratinocyte-specific
Ppp6c
conditional knockout mice and performed two-stage skin carcinogenesis analysis.
Ppp6c
deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1β was enhanced in
Ppp6c
-deficient keratinocytes. Overall, we conclude that
Ppp6c
deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice.</description><subject>13/95</subject><subject>14/63</subject><subject>45/41</subject><subject>631/67/581</subject><subject>64/60</subject><subject>9,10-Dimethyl-1,2-benzanthracene</subject><subject>96/1</subject><subject>Acetic acid</subject><subject>Animals</subject><subject>Anthracene</subject><subject>Apoptosis</subject><subject>Carcinogenesis</subject><subject>Carcinogenesis - metabolism</subject><subject>Cell Biology</subject><subject>Cells, Cultured</subject><subject>Gene mutations</subject><subject>Human Genetics</subject><subject>Internal Medicine</subject><subject>Keratinocytes</subject><subject>Keratinocytes - enzymology</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Melanoma</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CBA</subject><subject>Mice, Transgenic</subject><subject>Mutation</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Oncology</subject><subject>original-article</subject><subject>Papilloma</subject><subject>Phosphatase</subject><subject>Phosphatases</subject><subject>Phosphoprotein Phosphatases - genetics</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Protein phosphatase</subject><subject>Proteins</subject><subject>Raf protein</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Skin</subject><subject>Skin - enzymology</subject><subject>Skin - pathology</subject><subject>Skin cancer</subject><subject>Skin Neoplasms - chemically induced</subject><subject>Skin Neoplasms - enzymology</subject><subject>Studies</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Tumorigenesis</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kU1vVCEUhkmjsWN117W5idvekc8LLKcfVpMau6hrAtzDlNoLU7iz6L-XyVSrSWNYkLznOYdDHoSOCV4SzNSnnPySYsKXTKsDtCBcDr0Qmr9CC6wF7jVl9BC9rfUOYyw1pm_QIRVcDZzxBbpeuZLXdo45dTl0m5JniKnb3Oa6ubWzrdANu3Rqee3qz1bztviY8hoS1Fi7mMath7Fzj935t9PVO_Q62PsK75_uI_Tj88XN2Zf-6vvl17PVVe-FZnMvPQgIlAsdtGIK-8C5Gz3zo3beYk6cknak4JhgXnDqBAbHg-AcU0KHkR2hj_u5bbmHLdTZ3OVtSe1JQxkjA5MCi_9RRGKp-MAIfabW9h5MTCHPxfopVm9WnCoqBZGqUcsXqHZGmKLPCUJs-T8NJ_sGX3KtBYLZlDjZ8mgINjt3prkzO3emuWv4h6ddt26C8Q_8W1YD-j1QWymtofz1mZcG_gLx5aDM</recordid><startdate>20150827</startdate><enddate>20150827</enddate><creator>Hayashi, 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of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA</title><author>Hayashi, K ; Momoi, Y ; Tanuma, N ; Kishimoto, A ; Ogoh, H ; Kato, H ; Suzuki, M ; Sakamoto, Y ; Inoue, Y ; Nomura, M ; Kiyonari, H ; Sakayori, M ; Fukamachi, K ; Kakugawa, Y ; Yamashita, Y ; Ito, S ; Sato, I ; Suzuki, A ; Nishio, M ; Suganuma, M ; Watanabe, T ; Shima, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-7ce5ef2459f98380cf44bdc3cd9bca041b87ad2eb353c542b50eb4f54402126d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>13/95</topic><topic>14/63</topic><topic>45/41</topic><topic>631/67/581</topic><topic>64/60</topic><topic>9,10-Dimethyl-1,2-benzanthracene</topic><topic>96/1</topic><topic>Acetic acid</topic><topic>Animals</topic><topic>Anthracene</topic><topic>Apoptosis</topic><topic>Carcinogenesis</topic><topic>Carcinogenesis - metabolism</topic><topic>Cell Biology</topic><topic>Cells, Cultured</topic><topic>Gene mutations</topic><topic>Human Genetics</topic><topic>Internal Medicine</topic><topic>Keratinocytes</topic><topic>Keratinocytes - enzymology</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Melanoma</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred CBA</topic><topic>Mice, Transgenic</topic><topic>Mutation</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Oncology</topic><topic>original-article</topic><topic>Papilloma</topic><topic>Phosphatase</topic><topic>Phosphatases</topic><topic>Phosphoprotein Phosphatases - genetics</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Protein phosphatase</topic><topic>Proteins</topic><topic>Raf protein</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Skin</topic><topic>Skin - enzymology</topic><topic>Skin - pathology</topic><topic>Skin cancer</topic><topic>Skin Neoplasms - chemically 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Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hayashi, K</au><au>Momoi, Y</au><au>Tanuma, N</au><au>Kishimoto, A</au><au>Ogoh, H</au><au>Kato, H</au><au>Suzuki, M</au><au>Sakamoto, Y</au><au>Inoue, Y</au><au>Nomura, M</au><au>Kiyonari, H</au><au>Sakayori, M</au><au>Fukamachi, K</au><au>Kakugawa, Y</au><au>Yamashita, Y</au><au>Ito, S</au><au>Sato, I</au><au>Suzuki, A</au><au>Nishio, M</au><au>Suganuma, M</au><au>Watanabe, T</au><au>Shima, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2015-08-27</date><risdate>2015</risdate><volume>34</volume><issue>35</issue><spage>4647</spage><epage>4655</epage><pages>4647-4655</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 (
Ppp6c
) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of
Ppp6c
in carcinogenesis, we generated skin keratinocyte-specific
Ppp6c
conditional knockout mice and performed two-stage skin carcinogenesis analysis.
Ppp6c
deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1β was enhanced in
Ppp6c
-deficient keratinocytes. Overall, we conclude that
Ppp6c
deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25486434</pmid><doi>10.1038/onc.2014.398</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2015-08, Vol.34 (35), p.4647-4655 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_journals_2331637505 |
| source | MEDLINE; Nature; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | 13/95 14/63 45/41 631/67/581 64/60 9,10-Dimethyl-1,2-benzanthracene 96/1 Acetic acid Animals Anthracene Apoptosis Carcinogenesis Carcinogenesis - metabolism Cell Biology Cells, Cultured Gene mutations Human Genetics Internal Medicine Keratinocytes Keratinocytes - enzymology Medicine Medicine & Public Health Melanoma Mice, Inbred C57BL Mice, Inbred CBA Mice, Transgenic Mutation NF-kappa B - metabolism NF-κB protein Oncology original-article Papilloma Phosphatase Phosphatases Phosphoprotein Phosphatases - genetics Phosphoprotein Phosphatases - metabolism Protein phosphatase Proteins Raf protein Rodents Signal Transduction Skin Skin - enzymology Skin - pathology Skin cancer Skin Neoplasms - chemically induced Skin Neoplasms - enzymology Studies Tumor necrosis factor-TNF Tumor necrosis factor-α Tumorigenesis |
| title | Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA |
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