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
Hauptverfasser: Lachmann, Margit, Gelbmann, Dieter, Kálmán, Endre, Polgár, Beata, Buschle, Michael, von Gabain, Alexander, Szekeres‐Barthó, Júlia, Nagy, Eszter
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container_issue 1
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container_title International journal of cancer
container_volume 112
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. 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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. 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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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source MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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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