PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome
PIBF was previously identified as a 34 kDa immunomodulatory molecule secreted by pregnancy lymphocytes and is thought to play a crucial role in preventing rejection of the embryo by the maternal immune response. Recent data suggested that PIBF protein was also expressed by the progesterone receptor...
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Veröffentlicht in: | International journal of cancer 2004-10, Vol.112 (1), p.51-60 |
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container_title | International journal of cancer |
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creator | Lachmann, Margit Gelbmann, Dieter Kálmán, Endre Polgár, Beata Buschle, Michael von Gabain, Alexander Szekeres‐Barthó, Júlia Nagy, Eszter |
description | PIBF was previously identified as a 34 kDa immunomodulatory molecule secreted by pregnancy lymphocytes and is thought to play a crucial role in preventing rejection of the embryo by the maternal immune response. Recent data suggested that PIBF protein was also expressed by the progesterone receptor (PR) positive MCF‐7 breast tumor cell line. Therefore our study was designed to analyze the expression of PIBF in malignant cell lines and primary tumors both at the mRNA and protein levels. RNA expression analyses of several human cell lines with different tissue origin and paired human tumor/normal tissues, as well as of several PR+ and PR− breast tumors revealed that PIBF mRNA was overexpressed in highly proliferating cells independent of the presence of PR. In addition to the full‐length PIBF mRNA encoding for a 90 kDa protein, several alternatively spliced species were detected, all resulting from perfect exon skipping. The most frequently identified splice variant is predicted to encode for an approximately 35 kDa protein. Immunofluorescence microscopy revealed a centrosomal localization for the full‐length PIBF, while the 35 kDa form showed a diffuse cytoplasmic staining. These data, together with the identification of the PIBF gene in the chromosomal region associated with breast cancer susceptibility, reveal a strong parallel with known tumor suppressor proteins, such as BRCA1 and p53 having the same centrosomal localization. Given the notion that a number of proteins shown to be involved in tumorigenesis are associated with the centrosome and disturbed centrosome function causes unequal segregation of chromosomes, studies to evaluate whether or not PIBF that is highly expressed in tumors is directly involved in tumorigenesis are thus warranted. © 2004 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/ijc.20326 |
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Recent data suggested that PIBF protein was also expressed by the progesterone receptor (PR) positive MCF‐7 breast tumor cell line. Therefore our study was designed to analyze the expression of PIBF in malignant cell lines and primary tumors both at the mRNA and protein levels. RNA expression analyses of several human cell lines with different tissue origin and paired human tumor/normal tissues, as well as of several PR+ and PR− breast tumors revealed that PIBF mRNA was overexpressed in highly proliferating cells independent of the presence of PR. In addition to the full‐length PIBF mRNA encoding for a 90 kDa protein, several alternatively spliced species were detected, all resulting from perfect exon skipping. The most frequently identified splice variant is predicted to encode for an approximately 35 kDa protein. Immunofluorescence microscopy revealed a centrosomal localization for the full‐length PIBF, while the 35 kDa form showed a diffuse cytoplasmic staining. These data, together with the identification of the PIBF gene in the chromosomal region associated with breast cancer susceptibility, reveal a strong parallel with known tumor suppressor proteins, such as BRCA1 and p53 having the same centrosomal localization. Given the notion that a number of proteins shown to be involved in tumorigenesis are associated with the centrosome and disturbed centrosome function causes unequal segregation of chromosomes, studies to evaluate whether or not PIBF that is highly expressed in tumors is directly involved in tumorigenesis are thus warranted. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.20326</identifier><identifier>PMID: 15305375</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Alternative Splicing ; Biological and medical sciences ; Biomarkers - chemistry ; Breast - metabolism ; Breast - pathology ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Case-Control Studies ; Cell Division ; centrosomal localization ; Centrosome - metabolism ; Centrosome - pathology ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; Mammary gland diseases ; Medical sciences ; PIBF ; Pregnancy Proteins - genetics ; Pregnancy Proteins - metabolism ; Receptors, Estrogen - metabolism ; Receptors, Progesterone - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Subcellular Fractions - metabolism ; Subcellular Fractions - pathology ; Suppressor Factors, Immunologic - genetics ; Suppressor Factors, Immunologic - metabolism ; Tumor Cells, Cultured ; Tumors</subject><ispartof>International journal of cancer, 2004-10, Vol.112 (1), p.51-60</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4506-1053c529f7502885035abf8b0550e2ea6c45d3593ef5f21920de5edef8c9a2493</citedby><cites>FETCH-LOGICAL-c4506-1053c529f7502885035abf8b0550e2ea6c45d3593ef5f21920de5edef8c9a2493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.20326$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.20326$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16120509$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15305375$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lachmann, Margit</creatorcontrib><creatorcontrib>Gelbmann, Dieter</creatorcontrib><creatorcontrib>Kálmán, Endre</creatorcontrib><creatorcontrib>Polgár, Beata</creatorcontrib><creatorcontrib>Buschle, Michael</creatorcontrib><creatorcontrib>von Gabain, Alexander</creatorcontrib><creatorcontrib>Szekeres‐Barthó, Júlia</creatorcontrib><creatorcontrib>Nagy, Eszter</creatorcontrib><title>PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>PIBF was previously identified as a 34 kDa immunomodulatory molecule secreted by pregnancy lymphocytes and is thought to play a crucial role in preventing rejection of the embryo by the maternal immune response. Recent data suggested that PIBF protein was also expressed by the progesterone receptor (PR) positive MCF‐7 breast tumor cell line. Therefore our study was designed to analyze the expression of PIBF in malignant cell lines and primary tumors both at the mRNA and protein levels. RNA expression analyses of several human cell lines with different tissue origin and paired human tumor/normal tissues, as well as of several PR+ and PR− breast tumors revealed that PIBF mRNA was overexpressed in highly proliferating cells independent of the presence of PR. In addition to the full‐length PIBF mRNA encoding for a 90 kDa protein, several alternatively spliced species were detected, all resulting from perfect exon skipping. The most frequently identified splice variant is predicted to encode for an approximately 35 kDa protein. Immunofluorescence microscopy revealed a centrosomal localization for the full‐length PIBF, while the 35 kDa form showed a diffuse cytoplasmic staining. These data, together with the identification of the PIBF gene in the chromosomal region associated with breast cancer susceptibility, reveal a strong parallel with known tumor suppressor proteins, such as BRCA1 and p53 having the same centrosomal localization. Given the notion that a number of proteins shown to be involved in tumorigenesis are associated with the centrosome and disturbed centrosome function causes unequal segregation of chromosomes, studies to evaluate whether or not PIBF that is highly expressed in tumors is directly involved in tumorigenesis are thus warranted. © 2004 Wiley‐Liss, Inc.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Alternative Splicing</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - chemistry</subject><subject>Breast - metabolism</subject><subject>Breast - pathology</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Case-Control Studies</subject><subject>Cell Division</subject><subject>centrosomal localization</subject><subject>Centrosome - metabolism</subject><subject>Centrosome - pathology</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>PIBF</subject><subject>Pregnancy Proteins - genetics</subject><subject>Pregnancy Proteins - metabolism</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Receptors, Progesterone - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Subcellular Fractions - metabolism</subject><subject>Subcellular Fractions - pathology</subject><subject>Suppressor Factors, Immunologic - genetics</subject><subject>Suppressor Factors, Immunologic - metabolism</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFvEzEQhS1ERUPgwB9AvoDaw7Zje2e9eywRpakqwQHOK8c7Tlw262BvKDnw33FIpJ6gJx_m85v35jH2RsCFAJCX_t5eSFCyesYmAhpdgBT4nE3yDAotVHXKXqZ0DyAEQvmCnQpUgErjhP3-Mv9wzc82MSwpjRTDQNwP3dZSxxd9sN_9sOTO2DHEc-4TDz8p0q9NpJQy4Qe-8stVv-NZoPeOohn3Hyz1feJm6LhJKVhvxgw_-HHFxxXl6TDGkMKaXrETZ_pEr4_vlH27_vh1dlPcff40n13dFbZEqAqRzVqUjdMIsq4RFJqFqxeACCTJVBnrFDaKHDopGgkdIXXkatsYWTZqyt4fdLPNH9sctF37tDdpBgrb1FaV1rrMV5mys_-CotZYowStntQUuqplKWQGzw-gzaFTJNduol-buGsFtPv-2txf-7e_zL49im4Xa-oeyWNhGXh3BEyypnfRDNanR64SEhD2iS8P3IPvaffvje38dnZY_QeflrGg</recordid><startdate>20041020</startdate><enddate>20041020</enddate><creator>Lachmann, Margit</creator><creator>Gelbmann, Dieter</creator><creator>Kálmán, Endre</creator><creator>Polgár, Beata</creator><creator>Buschle, Michael</creator><creator>von Gabain, Alexander</creator><creator>Szekeres‐Barthó, Júlia</creator><creator>Nagy, Eszter</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>IQODW</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>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20041020</creationdate><title>PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome</title><author>Lachmann, Margit ; Gelbmann, Dieter ; Kálmán, Endre ; Polgár, Beata ; Buschle, Michael ; von Gabain, Alexander ; Szekeres‐Barthó, Júlia ; Nagy, Eszter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4506-1053c529f7502885035abf8b0550e2ea6c45d3593ef5f21920de5edef8c9a2493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Alternative Splicing</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - chemistry</topic><topic>Breast - metabolism</topic><topic>Breast - pathology</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Case-Control Studies</topic><topic>Cell Division</topic><topic>centrosomal localization</topic><topic>Centrosome - metabolism</topic><topic>Centrosome - pathology</topic><topic>Female</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>PIBF</topic><topic>Pregnancy Proteins - genetics</topic><topic>Pregnancy Proteins - metabolism</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Receptors, Progesterone - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Subcellular Fractions - metabolism</topic><topic>Subcellular Fractions - pathology</topic><topic>Suppressor Factors, Immunologic - genetics</topic><topic>Suppressor Factors, Immunologic - metabolism</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lachmann, Margit</creatorcontrib><creatorcontrib>Gelbmann, Dieter</creatorcontrib><creatorcontrib>Kálmán, Endre</creatorcontrib><creatorcontrib>Polgár, Beata</creatorcontrib><creatorcontrib>Buschle, Michael</creatorcontrib><creatorcontrib>von Gabain, Alexander</creatorcontrib><creatorcontrib>Szekeres‐Barthó, Júlia</creatorcontrib><creatorcontrib>Nagy, Eszter</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>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lachmann, Margit</au><au>Gelbmann, Dieter</au><au>Kálmán, Endre</au><au>Polgár, Beata</au><au>Buschle, Michael</au><au>von Gabain, Alexander</au><au>Szekeres‐Barthó, Júlia</au><au>Nagy, Eszter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2004-10-20</date><risdate>2004</risdate><volume>112</volume><issue>1</issue><spage>51</spage><epage>60</epage><pages>51-60</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>PIBF was previously identified as a 34 kDa immunomodulatory molecule secreted by pregnancy lymphocytes and is thought to play a crucial role in preventing rejection of the embryo by the maternal immune response. Recent data suggested that PIBF protein was also expressed by the progesterone receptor (PR) positive MCF‐7 breast tumor cell line. Therefore our study was designed to analyze the expression of PIBF in malignant cell lines and primary tumors both at the mRNA and protein levels. RNA expression analyses of several human cell lines with different tissue origin and paired human tumor/normal tissues, as well as of several PR+ and PR− breast tumors revealed that PIBF mRNA was overexpressed in highly proliferating cells independent of the presence of PR. In addition to the full‐length PIBF mRNA encoding for a 90 kDa protein, several alternatively spliced species were detected, all resulting from perfect exon skipping. The most frequently identified splice variant is predicted to encode for an approximately 35 kDa protein. Immunofluorescence microscopy revealed a centrosomal localization for the full‐length PIBF, while the 35 kDa form showed a diffuse cytoplasmic staining. These data, together with the identification of the PIBF gene in the chromosomal region associated with breast cancer susceptibility, reveal a strong parallel with known tumor suppressor proteins, such as BRCA1 and p53 having the same centrosomal localization. Given the notion that a number of proteins shown to be involved in tumorigenesis are associated with the centrosome and disturbed centrosome function causes unequal segregation of chromosomes, studies to evaluate whether or not PIBF that is highly expressed in tumors is directly involved in tumorigenesis are thus warranted. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15305375</pmid><doi>10.1002/ijc.20326</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenocarcinoma - genetics Adenocarcinoma - metabolism Adenocarcinoma - pathology Alternative Splicing Biological and medical sciences Biomarkers - chemistry Breast - metabolism Breast - pathology Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Case-Control Studies Cell Division centrosomal localization Centrosome - metabolism Centrosome - pathology Female Gynecology. Andrology. Obstetrics Humans Mammary gland diseases Medical sciences PIBF Pregnancy Proteins - genetics Pregnancy Proteins - metabolism Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Subcellular Fractions - metabolism Subcellular Fractions - pathology Suppressor Factors, Immunologic - genetics Suppressor Factors, Immunologic - metabolism Tumor Cells, Cultured Tumors |
title | PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome |
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