Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation
PTEN is a tumor suppressor gene mutated in many human cancers. We used the Cre-loxP system to generate a keratinocyte-specific null mutation of Pten in mice (k5Pten(flox/flox) mice). k5Pten(flox/flox) mice exhibit wrinkled skin because of epidermal hyperplasia and hyperkeratosis and ruffled, shaggy,...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2003-02, Vol.63 (3), p.674-681 |
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| creator | SUZUKI, Akira ITAMI, Satoshi TAK WAH MAK NAKANO, Toru OHISHI, Minako HAMADA, Koichi INOUE, Tae KOMAZAWA, Nobuyasu SENOO, Haruki SASAKI, Takehiko TAKEDA, Junji MANABE, Motomu |
| description | PTEN is a tumor suppressor gene mutated in many human cancers. We used the Cre-loxP system to generate a keratinocyte-specific null mutation of Pten in mice (k5Pten(flox/flox) mice). k5Pten(flox/flox) mice exhibit wrinkled skin because of epidermal hyperplasia and hyperkeratosis and ruffled, shaggy, and curly hair. Histological examination revealed that skin morphogenesis is accelerated in k5Pten(flox/flox) mice. Within 3 weeks of birth, 90% of k5Pten(flox/flox) mice die of malnutrition possibly caused by hyperkeratosis of the esophagus. All k5Pten(flox/flox) mice develop spontaneous tumors within 8.5 months of birth, and chemical treatment accelerates the onset of tumors. k5Pten(flox/flox) keratinocytes are hyperproliferative and resistant to apoptosis and show increased activation of the Pten downstream signaling mediators Akt/protein kinase B (PKB) and extracellular signal-regulated kinase. Pten is thus an important regulator of normal development and oncogenesis in the skin. |
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We used the Cre-loxP system to generate a keratinocyte-specific null mutation of Pten in mice (k5Pten(flox/flox) mice). k5Pten(flox/flox) mice exhibit wrinkled skin because of epidermal hyperplasia and hyperkeratosis and ruffled, shaggy, and curly hair. Histological examination revealed that skin morphogenesis is accelerated in k5Pten(flox/flox) mice. Within 3 weeks of birth, 90% of k5Pten(flox/flox) mice die of malnutrition possibly caused by hyperkeratosis of the esophagus. All k5Pten(flox/flox) mice develop spontaneous tumors within 8.5 months of birth, and chemical treatment accelerates the onset of tumors. k5Pten(flox/flox) keratinocytes are hyperproliferative and resistant to apoptosis and show increased activation of the Pten downstream signaling mediators Akt/protein kinase B (PKB) and extracellular signal-regulated kinase. Pten is thus an important regulator of normal development and oncogenesis in the skin.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 12566313</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Apoptosis - physiology ; Biological and medical sciences ; Cell Division - physiology ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Enzyme Activation ; Female ; Fundamental and applied biological sciences. Psychology ; Hair Follicle - cytology ; Hyperplasia - enzymology ; Hyperplasia - genetics ; Keratinocytes - enzymology ; Keratinocytes - pathology ; Keratinocytes - physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitogen-Activated Protein Kinases - metabolism ; Molecular and cellular biology ; Phosphoric Monoester Hydrolases - biosynthesis ; Phosphoric Monoester Hydrolases - genetics ; Phosphoric Monoester Hydrolases - physiology ; Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-akt ; PTEN Phosphohydrolase ; Skin - enzymology ; Skin - pathology ; Skin Abnormalities - enzymology ; Skin Abnormalities - genetics ; Skin Abnormalities - pathology ; Skin Neoplasms - enzymology ; Skin Neoplasms - genetics ; Tumor Suppressor Proteins - biosynthesis ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - physiology</subject><ispartof>Cancer research (Chicago, Ill.), 2003-02, Vol.63 (3), p.674-681</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14505209$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12566313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SUZUKI, Akira</creatorcontrib><creatorcontrib>ITAMI, Satoshi</creatorcontrib><creatorcontrib>TAK WAH MAK</creatorcontrib><creatorcontrib>NAKANO, Toru</creatorcontrib><creatorcontrib>OHISHI, Minako</creatorcontrib><creatorcontrib>HAMADA, Koichi</creatorcontrib><creatorcontrib>INOUE, Tae</creatorcontrib><creatorcontrib>KOMAZAWA, Nobuyasu</creatorcontrib><creatorcontrib>SENOO, Haruki</creatorcontrib><creatorcontrib>SASAKI, Takehiko</creatorcontrib><creatorcontrib>TAKEDA, Junji</creatorcontrib><creatorcontrib>MANABE, Motomu</creatorcontrib><title>Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>PTEN is a tumor suppressor gene mutated in many human cancers. We used the Cre-loxP system to generate a keratinocyte-specific null mutation of Pten in mice (k5Pten(flox/flox) mice). k5Pten(flox/flox) mice exhibit wrinkled skin because of epidermal hyperplasia and hyperkeratosis and ruffled, shaggy, and curly hair. Histological examination revealed that skin morphogenesis is accelerated in k5Pten(flox/flox) mice. Within 3 weeks of birth, 90% of k5Pten(flox/flox) mice die of malnutrition possibly caused by hyperkeratosis of the esophagus. All k5Pten(flox/flox) mice develop spontaneous tumors within 8.5 months of birth, and chemical treatment accelerates the onset of tumors. k5Pten(flox/flox) keratinocytes are hyperproliferative and resistant to apoptosis and show increased activation of the Pten downstream signaling mediators Akt/protein kinase B (PKB) and extracellular signal-regulated kinase. Pten is thus an important regulator of normal development and oncogenesis in the skin.</description><subject>Animals</subject><subject>Apoptosis - physiology</subject><subject>Biological and medical sciences</subject><subject>Cell Division - physiology</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Enzyme Activation</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hair Follicle - cytology</subject><subject>Hyperplasia - enzymology</subject><subject>Hyperplasia - genetics</subject><subject>Keratinocytes - enzymology</subject><subject>Keratinocytes - pathology</subject><subject>Keratinocytes - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Molecular and cellular biology</subject><subject>Phosphoric Monoester Hydrolases - biosynthesis</subject><subject>Phosphoric Monoester Hydrolases - genetics</subject><subject>Phosphoric Monoester Hydrolases - physiology</subject><subject>Protein-Serine-Threonine Kinases</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-akt</subject><subject>PTEN Phosphohydrolase</subject><subject>Skin - enzymology</subject><subject>Skin - pathology</subject><subject>Skin Abnormalities - enzymology</subject><subject>Skin Abnormalities - genetics</subject><subject>Skin Abnormalities - pathology</subject><subject>Skin Neoplasms - enzymology</subject><subject>Skin Neoplasms - genetics</subject><subject>Tumor Suppressor Proteins - biosynthesis</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - physiology</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LxDAQhoMo7rr6FyQXPVnIR9OPo4hfuKAHPZfZdGIjaVqT9rBn_7hZXPHoaWZeHp4Z5oAsuZJVVua5OiRLxliVqbwUC3IS40caFWfqmCy4UEUhuVySrycMMFk_6O2EWRxRW2M1fZnQ0xZTa9HrLQ0YZzdFaj3F0bYYenC0244YRgfRwhUFrdHtXNjSDmygZnDOaoe0H8LYDe_oMdpIwbd0mlOWgGSZ7OBPyZEBF_FsX1fk7e729eYhWz_fP95cr7NOMjZlBoREZRAKZJVutTLGsMKovELOWakEkxrKUpi8bFuxAS44JGpTyLpQNSvlilz-eMcwfM4Yp6a3MV3twOMwx6YUdV1VufwX5FUlit2-FTnfg_Omx7YZg-0hbJvf_ybgYg9A1OBMAK9t_ONyxZKnlt9-aYgI</recordid><startdate>20030201</startdate><enddate>20030201</enddate><creator>SUZUKI, Akira</creator><creator>ITAMI, Satoshi</creator><creator>TAK WAH MAK</creator><creator>NAKANO, Toru</creator><creator>OHISHI, Minako</creator><creator>HAMADA, Koichi</creator><creator>INOUE, Tae</creator><creator>KOMAZAWA, Nobuyasu</creator><creator>SENOO, Haruki</creator><creator>SASAKI, Takehiko</creator><creator>TAKEDA, Junji</creator><creator>MANABE, Motomu</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20030201</creationdate><title>Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation</title><author>SUZUKI, Akira ; ITAMI, Satoshi ; TAK WAH MAK ; NAKANO, Toru ; OHISHI, Minako ; HAMADA, Koichi ; INOUE, Tae ; KOMAZAWA, Nobuyasu ; SENOO, Haruki ; SASAKI, Takehiko ; TAKEDA, Junji ; MANABE, Motomu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h300t-fa23e5fea6e08cdc5fff06f548e11075203ca772f47dd2ba121adc5b639659073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Apoptosis - physiology</topic><topic>Biological and medical sciences</topic><topic>Cell Division - physiology</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Enzyme Activation</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hair Follicle - cytology</topic><topic>Hyperplasia - enzymology</topic><topic>Hyperplasia - genetics</topic><topic>Keratinocytes - enzymology</topic><topic>Keratinocytes - pathology</topic><topic>Keratinocytes - physiology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Molecular and cellular biology</topic><topic>Phosphoric Monoester Hydrolases - biosynthesis</topic><topic>Phosphoric Monoester Hydrolases - genetics</topic><topic>Phosphoric Monoester Hydrolases - physiology</topic><topic>Protein-Serine-Threonine Kinases</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-akt</topic><topic>PTEN Phosphohydrolase</topic><topic>Skin - enzymology</topic><topic>Skin - pathology</topic><topic>Skin Abnormalities - enzymology</topic><topic>Skin Abnormalities - genetics</topic><topic>Skin Abnormalities - pathology</topic><topic>Skin Neoplasms - enzymology</topic><topic>Skin Neoplasms - genetics</topic><topic>Tumor Suppressor Proteins - biosynthesis</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SUZUKI, Akira</creatorcontrib><creatorcontrib>ITAMI, Satoshi</creatorcontrib><creatorcontrib>TAK WAH MAK</creatorcontrib><creatorcontrib>NAKANO, Toru</creatorcontrib><creatorcontrib>OHISHI, Minako</creatorcontrib><creatorcontrib>HAMADA, Koichi</creatorcontrib><creatorcontrib>INOUE, Tae</creatorcontrib><creatorcontrib>KOMAZAWA, Nobuyasu</creatorcontrib><creatorcontrib>SENOO, Haruki</creatorcontrib><creatorcontrib>SASAKI, Takehiko</creatorcontrib><creatorcontrib>TAKEDA, Junji</creatorcontrib><creatorcontrib>MANABE, Motomu</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SUZUKI, Akira</au><au>ITAMI, Satoshi</au><au>TAK WAH MAK</au><au>NAKANO, Toru</au><au>OHISHI, Minako</au><au>HAMADA, Koichi</au><au>INOUE, Tae</au><au>KOMAZAWA, Nobuyasu</au><au>SENOO, Haruki</au><au>SASAKI, Takehiko</au><au>TAKEDA, Junji</au><au>MANABE, Motomu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2003-02-01</date><risdate>2003</risdate><volume>63</volume><issue>3</issue><spage>674</spage><epage>681</epage><pages>674-681</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>PTEN is a tumor suppressor gene mutated in many human cancers. We used the Cre-loxP system to generate a keratinocyte-specific null mutation of Pten in mice (k5Pten(flox/flox) mice). k5Pten(flox/flox) mice exhibit wrinkled skin because of epidermal hyperplasia and hyperkeratosis and ruffled, shaggy, and curly hair. Histological examination revealed that skin morphogenesis is accelerated in k5Pten(flox/flox) mice. Within 3 weeks of birth, 90% of k5Pten(flox/flox) mice die of malnutrition possibly caused by hyperkeratosis of the esophagus. All k5Pten(flox/flox) mice develop spontaneous tumors within 8.5 months of birth, and chemical treatment accelerates the onset of tumors. k5Pten(flox/flox) keratinocytes are hyperproliferative and resistant to apoptosis and show increased activation of the Pten downstream signaling mediators Akt/protein kinase B (PKB) and extracellular signal-regulated kinase. Pten is thus an important regulator of normal development and oncogenesis in the skin.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>12566313</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 2003-02, Vol.63 (3), p.674-681 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Apoptosis - physiology Biological and medical sciences Cell Division - physiology Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Enzyme Activation Female Fundamental and applied biological sciences. Psychology Hair Follicle - cytology Hyperplasia - enzymology Hyperplasia - genetics Keratinocytes - enzymology Keratinocytes - pathology Keratinocytes - physiology Male Mice Mice, Inbred C57BL Mice, Transgenic Mitogen-Activated Protein Kinases - metabolism Molecular and cellular biology Phosphoric Monoester Hydrolases - biosynthesis Phosphoric Monoester Hydrolases - genetics Phosphoric Monoester Hydrolases - physiology Protein-Serine-Threonine Kinases Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase Skin - enzymology Skin - pathology Skin Abnormalities - enzymology Skin Abnormalities - genetics Skin Abnormalities - pathology Skin Neoplasms - enzymology Skin Neoplasms - genetics Tumor Suppressor Proteins - biosynthesis Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - physiology |
| title | Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation |
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