Expression of Sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium
The aim of the present study was to determine the expression profile of the hedgehog (Hh) signaling molecules in normal, hyperplastic, and carcinomatous uterine endometrium. For this purpose, 271 endometrial tissue samples, (62 of normal endometrium, 127 of endometrial hyperplasias, and 82 endometri...
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| Veröffentlicht in: | Pathology international 2009-05, Vol.59 (5), p.279-287 |
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| creator | Kim, Kyung Hee Kim, Jin Man Choi, Yoon-La Shin, Young Kee Lee, Ho-chang Seong, In Ock Kim, Bum Kyung Chae, Seoung Wan Chung, Yun-Shin Kim, Seok-Hyung |
| description | The aim of the present study was to determine the expression profile of the hedgehog (Hh) signaling molecules in normal, hyperplastic, and carcinomatous uterine endometrium. For this purpose, 271 endometrial tissue samples, (62 of normal endometrium, 127 of endometrial hyperplasias, and 82 endometrial adenocarcinomas) were studied using antibodies recognizing Hh‐related signaling proteins, such as, sonic hedgehog (Shh), Patched (PTCH), Smoothened (Smo), Suppressor of fused [Su(Fu)], Gli‐1, Gli‐2, and Gli‐3 by immunohistochemistry. The mRNA expression of these molecules was also assessed on reverse transcription–polymerase chain reaction. In the normal endometrium, the expression of Hh signaling molecules was generally downregulated except for Su(Fu), Gli‐2, and Shh. In particular, the expression of both PTCH and Smo was very low or almost absent. Overall expression of Hh signaling molecules increased in hyperplastic endometrium; in particular, PTCH and Smo were significantly highly expressed in complex and atypical hyperplasia. In carcinoma samples extensive alterations were observed in the expression pattern of the signaling molecules. Nuclear Gli‐2, cytoplasmic Gli‐3, and Su(Fu) were overexpressed, whereas Shh, PTCH, and Smo expression were significantly reduced compared with the hyperplastic endometrium. The results suggest that the alteration of Hh signaling may be implicated in tumorigenesis of the endometrium. |
| doi_str_mv | 10.1111/j.1440-1827.2009.02366.x |
| format | Article |
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For this purpose, 271 endometrial tissue samples, (62 of normal endometrium, 127 of endometrial hyperplasias, and 82 endometrial adenocarcinomas) were studied using antibodies recognizing Hh‐related signaling proteins, such as, sonic hedgehog (Shh), Patched (PTCH), Smoothened (Smo), Suppressor of fused [Su(Fu)], Gli‐1, Gli‐2, and Gli‐3 by immunohistochemistry. The mRNA expression of these molecules was also assessed on reverse transcription–polymerase chain reaction. In the normal endometrium, the expression of Hh signaling molecules was generally downregulated except for Su(Fu), Gli‐2, and Shh. In particular, the expression of both PTCH and Smo was very low or almost absent. Overall expression of Hh signaling molecules increased in hyperplastic endometrium; in particular, PTCH and Smo were significantly highly expressed in complex and atypical hyperplasia. In carcinoma samples extensive alterations were observed in the expression pattern of the signaling molecules. Nuclear Gli‐2, cytoplasmic Gli‐3, and Su(Fu) were overexpressed, whereas Shh, PTCH, and Smo expression were significantly reduced compared with the hyperplastic endometrium. The results suggest that the alteration of Hh signaling may be implicated in tumorigenesis of the endometrium.</description><identifier>ISSN: 1320-5463</identifier><identifier>EISSN: 1440-1827</identifier><identifier>DOI: 10.1111/j.1440-1827.2009.02366.x</identifier><identifier>PMID: 19432668</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>adenocarcinoma ; Biomarkers, Tumor - analysis ; Cell Nucleus - metabolism ; Cytoplasm - metabolism ; Endometrial Hyperplasia - genetics ; Endometrial Hyperplasia - metabolism ; Endometrial Neoplasms - genetics ; Endometrial Neoplasms - metabolism ; endometrium ; Endometrium - metabolism ; Female ; Gene Expression ; Gli protein ; hedgehog proteins ; Hedgehog Proteins - biosynthesis ; Hedgehog Proteins - genetics ; Humans ; hyperplasia ; Immunohistochemistry ; Kruppel-Like Transcription Factors - biosynthesis ; Kruppel-Like Transcription Factors - genetics ; Microdissection ; Nerve Tissue Proteins - biosynthesis ; Nerve Tissue Proteins - genetics ; Nuclear Proteins - biosynthesis ; Nuclear Proteins - genetics ; Patched Receptors ; Patched-1 Receptor ; Receptors, Cell Surface - biosynthesis ; Receptors, G-Protein-Coupled - biosynthesis ; Receptors, G-Protein-Coupled - genetics ; Repressor Proteins - biosynthesis ; Repressor Proteins - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Smoothened protein ; Smoothened Receptor ; sonic hedgehog protein ; Tissue Array Analysis ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Zinc Finger Protein GLI1 ; Zinc Finger Protein Gli2 ; Zinc Finger Protein Gli3</subject><ispartof>Pathology international, 2009-05, Vol.59 (5), p.279-287</ispartof><rights>2009 The Authors. Journal compilation © 2009 Japanese Society of Pathology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4586-72762a4dd7ef73f4822aac20cce76b596a704971eeeb847f02e796944eab1123</citedby><cites>FETCH-LOGICAL-c4586-72762a4dd7ef73f4822aac20cce76b596a704971eeeb847f02e796944eab1123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1440-1827.2009.02366.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1440-1827.2009.02366.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45552,45553</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19432668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Kyung Hee</creatorcontrib><creatorcontrib>Kim, Jin Man</creatorcontrib><creatorcontrib>Choi, Yoon-La</creatorcontrib><creatorcontrib>Shin, Young Kee</creatorcontrib><creatorcontrib>Lee, Ho-chang</creatorcontrib><creatorcontrib>Seong, In Ock</creatorcontrib><creatorcontrib>Kim, Bum Kyung</creatorcontrib><creatorcontrib>Chae, Seoung Wan</creatorcontrib><creatorcontrib>Chung, Yun-Shin</creatorcontrib><creatorcontrib>Kim, Seok-Hyung</creatorcontrib><title>Expression of Sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium</title><title>Pathology international</title><addtitle>Pathol Int</addtitle><description>The aim of the present study was to determine the expression profile of the hedgehog (Hh) signaling molecules in normal, hyperplastic, and carcinomatous uterine endometrium. For this purpose, 271 endometrial tissue samples, (62 of normal endometrium, 127 of endometrial hyperplasias, and 82 endometrial adenocarcinomas) were studied using antibodies recognizing Hh‐related signaling proteins, such as, sonic hedgehog (Shh), Patched (PTCH), Smoothened (Smo), Suppressor of fused [Su(Fu)], Gli‐1, Gli‐2, and Gli‐3 by immunohistochemistry. The mRNA expression of these molecules was also assessed on reverse transcription–polymerase chain reaction. In the normal endometrium, the expression of Hh signaling molecules was generally downregulated except for Su(Fu), Gli‐2, and Shh. In particular, the expression of both PTCH and Smo was very low or almost absent. Overall expression of Hh signaling molecules increased in hyperplastic endometrium; in particular, PTCH and Smo were significantly highly expressed in complex and atypical hyperplasia. In carcinoma samples extensive alterations were observed in the expression pattern of the signaling molecules. Nuclear Gli‐2, cytoplasmic Gli‐3, and Su(Fu) were overexpressed, whereas Shh, PTCH, and Smo expression were significantly reduced compared with the hyperplastic endometrium. The results suggest that the alteration of Hh signaling may be implicated in tumorigenesis of the endometrium.</description><subject>adenocarcinoma</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Cell Nucleus - metabolism</subject><subject>Cytoplasm - metabolism</subject><subject>Endometrial Hyperplasia - genetics</subject><subject>Endometrial Hyperplasia - metabolism</subject><subject>Endometrial Neoplasms - genetics</subject><subject>Endometrial Neoplasms - metabolism</subject><subject>endometrium</subject><subject>Endometrium - metabolism</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gli protein</subject><subject>hedgehog proteins</subject><subject>Hedgehog Proteins - biosynthesis</subject><subject>Hedgehog Proteins - genetics</subject><subject>Humans</subject><subject>hyperplasia</subject><subject>Immunohistochemistry</subject><subject>Kruppel-Like Transcription Factors - biosynthesis</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Microdissection</subject><subject>Nerve Tissue Proteins - biosynthesis</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nuclear Proteins - biosynthesis</subject><subject>Nuclear Proteins - genetics</subject><subject>Patched Receptors</subject><subject>Patched-1 Receptor</subject><subject>Receptors, Cell Surface - biosynthesis</subject><subject>Receptors, G-Protein-Coupled - biosynthesis</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Repressor Proteins - biosynthesis</subject><subject>Repressor Proteins - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Smoothened protein</subject><subject>Smoothened Receptor</subject><subject>sonic hedgehog protein</subject><subject>Tissue Array Analysis</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Zinc Finger Protein GLI1</subject><subject>Zinc Finger Protein Gli2</subject><subject>Zinc Finger Protein Gli3</subject><issn>1320-5463</issn><issn>1440-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1v1DAQhi1ERUvLX0A-cSLBX2snBw6otKVS1Q-1EtwsrzPZ9ZLYqZ2I3X-Pw67KtXOZkfw-49GDEKakpLm-bEoqBCloxVTJCKlLwriU5fYNOnl5eJtnzkixEJIfo_cpbQihikvyDh3TWnAmZXWC2ovtECElFzwOLX4M3lm8hmYF67DCya286Zxf4T50YKcOEnYe-xB7033G690AcehMGjNkfIOtidb50JsxTAmDb0IPY3RTf4aOWtMl-HDop-jp8uLp_Edxc3d1ff7tprBiUclCMSWZEU2joFW8FRVjxlhGrAUll4taGkVErSgALCuhWsJA1bIWAsySUsZP0af92iGG5wnSqHuXLHSd8ZAv0lIxLogiOVjtgzaGlCK0eoiuN3GnKdGzYr3Rs0k9m9SzYv1Psd5m9OPhj2nZQ_MfPDjNga_7wB_Xwe7Vi_X99e08Zb7Y8y6NsH3hTfyd7-dqoX_eXun7h8sH_qt-1N_5X7Chm0o</recordid><startdate>200905</startdate><enddate>200905</enddate><creator>Kim, Kyung Hee</creator><creator>Kim, Jin Man</creator><creator>Choi, Yoon-La</creator><creator>Shin, Young Kee</creator><creator>Lee, Ho-chang</creator><creator>Seong, In Ock</creator><creator>Kim, Bum Kyung</creator><creator>Chae, Seoung Wan</creator><creator>Chung, Yun-Shin</creator><creator>Kim, Seok-Hyung</creator><general>Blackwell Publishing Asia</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200905</creationdate><title>Expression of Sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium</title><author>Kim, Kyung Hee ; Kim, Jin Man ; Choi, Yoon-La ; Shin, Young Kee ; Lee, Ho-chang ; Seong, In Ock ; Kim, Bum Kyung ; Chae, Seoung Wan ; Chung, Yun-Shin ; Kim, Seok-Hyung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4586-72762a4dd7ef73f4822aac20cce76b596a704971eeeb847f02e796944eab1123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>adenocarcinoma</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Cell Nucleus - metabolism</topic><topic>Cytoplasm - metabolism</topic><topic>Endometrial Hyperplasia - genetics</topic><topic>Endometrial Hyperplasia - metabolism</topic><topic>Endometrial Neoplasms - genetics</topic><topic>Endometrial Neoplasms - metabolism</topic><topic>endometrium</topic><topic>Endometrium - metabolism</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gli protein</topic><topic>hedgehog proteins</topic><topic>Hedgehog Proteins - biosynthesis</topic><topic>Hedgehog Proteins - genetics</topic><topic>Humans</topic><topic>hyperplasia</topic><topic>Immunohistochemistry</topic><topic>Kruppel-Like Transcription Factors - biosynthesis</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Microdissection</topic><topic>Nerve Tissue Proteins - biosynthesis</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nuclear Proteins - biosynthesis</topic><topic>Nuclear Proteins - genetics</topic><topic>Patched Receptors</topic><topic>Patched-1 Receptor</topic><topic>Receptors, Cell Surface - biosynthesis</topic><topic>Receptors, G-Protein-Coupled - biosynthesis</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Repressor Proteins - biosynthesis</topic><topic>Repressor Proteins - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Smoothened protein</topic><topic>Smoothened Receptor</topic><topic>sonic hedgehog protein</topic><topic>Tissue Array Analysis</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Zinc Finger Protein GLI1</topic><topic>Zinc Finger Protein Gli2</topic><topic>Zinc Finger Protein Gli3</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Kyung Hee</creatorcontrib><creatorcontrib>Kim, Jin Man</creatorcontrib><creatorcontrib>Choi, Yoon-La</creatorcontrib><creatorcontrib>Shin, Young Kee</creatorcontrib><creatorcontrib>Lee, Ho-chang</creatorcontrib><creatorcontrib>Seong, In Ock</creatorcontrib><creatorcontrib>Kim, Bum Kyung</creatorcontrib><creatorcontrib>Chae, Seoung Wan</creatorcontrib><creatorcontrib>Chung, Yun-Shin</creatorcontrib><creatorcontrib>Kim, Seok-Hyung</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pathology international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Kyung Hee</au><au>Kim, Jin Man</au><au>Choi, Yoon-La</au><au>Shin, Young Kee</au><au>Lee, Ho-chang</au><au>Seong, In Ock</au><au>Kim, Bum Kyung</au><au>Chae, Seoung Wan</au><au>Chung, Yun-Shin</au><au>Kim, Seok-Hyung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of Sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium</atitle><jtitle>Pathology international</jtitle><addtitle>Pathol Int</addtitle><date>2009-05</date><risdate>2009</risdate><volume>59</volume><issue>5</issue><spage>279</spage><epage>287</epage><pages>279-287</pages><issn>1320-5463</issn><eissn>1440-1827</eissn><abstract>The aim of the present study was to determine the expression profile of the hedgehog (Hh) signaling molecules in normal, hyperplastic, and carcinomatous uterine endometrium. For this purpose, 271 endometrial tissue samples, (62 of normal endometrium, 127 of endometrial hyperplasias, and 82 endometrial adenocarcinomas) were studied using antibodies recognizing Hh‐related signaling proteins, such as, sonic hedgehog (Shh), Patched (PTCH), Smoothened (Smo), Suppressor of fused [Su(Fu)], Gli‐1, Gli‐2, and Gli‐3 by immunohistochemistry. The mRNA expression of these molecules was also assessed on reverse transcription–polymerase chain reaction. In the normal endometrium, the expression of Hh signaling molecules was generally downregulated except for Su(Fu), Gli‐2, and Shh. In particular, the expression of both PTCH and Smo was very low or almost absent. Overall expression of Hh signaling molecules increased in hyperplastic endometrium; in particular, PTCH and Smo were significantly highly expressed in complex and atypical hyperplasia. In carcinoma samples extensive alterations were observed in the expression pattern of the signaling molecules. Nuclear Gli‐2, cytoplasmic Gli‐3, and Su(Fu) were overexpressed, whereas Shh, PTCH, and Smo expression were significantly reduced compared with the hyperplastic endometrium. The results suggest that the alteration of Hh signaling may be implicated in tumorigenesis of the endometrium.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>19432668</pmid><doi>10.1111/j.1440-1827.2009.02366.x</doi><tpages>9</tpages></addata></record> |
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| subjects | adenocarcinoma Biomarkers, Tumor - analysis Cell Nucleus - metabolism Cytoplasm - metabolism Endometrial Hyperplasia - genetics Endometrial Hyperplasia - metabolism Endometrial Neoplasms - genetics Endometrial Neoplasms - metabolism endometrium Endometrium - metabolism Female Gene Expression Gli protein hedgehog proteins Hedgehog Proteins - biosynthesis Hedgehog Proteins - genetics Humans hyperplasia Immunohistochemistry Kruppel-Like Transcription Factors - biosynthesis Kruppel-Like Transcription Factors - genetics Microdissection Nerve Tissue Proteins - biosynthesis Nerve Tissue Proteins - genetics Nuclear Proteins - biosynthesis Nuclear Proteins - genetics Patched Receptors Patched-1 Receptor Receptors, Cell Surface - biosynthesis Receptors, G-Protein-Coupled - biosynthesis Receptors, G-Protein-Coupled - genetics Repressor Proteins - biosynthesis Repressor Proteins - genetics Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Smoothened protein Smoothened Receptor sonic hedgehog protein Tissue Array Analysis Transcription Factors - biosynthesis Transcription Factors - genetics Zinc Finger Protein GLI1 Zinc Finger Protein Gli2 Zinc Finger Protein Gli3 |
| title | Expression of Sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium |
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