{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:62246"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:62246","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Studien zur Expression von Klasse-1-Histon-Deacetylasen im humanen Endometrium sowie in Endometrium- und Mamma-Karzinomen","abstract":"Histone deacetylases (HDACs) deacetylate lysine residues of histone proteins. Thus the connection of the DNA to the histone octamer is strengthened, whereby gene expression is restrained. HDACs are involved in steroid-hormone dependent gene expression and into carcinogenesis. HDAC-inhibitors induce differentiation of endometrial and malignantly transformed cells. They inhibit proliferation and induce apoptosis in tumor cells. Thus HDACs are therapeutic targets. The expression of class I HDACs, HDAC1, 2 and 3, both in the endometrium and the mammary gland and in endometrial and breast carcinomas is largely unknown. Therefore, we assessed HDAC1, 2 and 3 expression in above tissues as well as in the T47D-breast cancer cell line, in consideration of the HDAC1 due to its role in cell cycle control. A hormonal regulation of the HDAC expression in the endometrium and in the T47D cell line was analyzed. The mRNA expression status in the human cyclic endometrium was examined with semiquantitative RT-PCR for HDAC1 and 3 and with the real-time PCR for HDAC2. By the western blot method the HDAC1, 2 and 3 protein expression status was also analyzed. With immunhistochemistry the localization and the intracellular distribution of the HDAC1 and 3 protein were defined. By means of immunhistochemistry HDAC1 protein expression in endometrial and breast carcinomas and in the T47D-cell line was examined. A hormonal regulated HDAC1 expression in the T47D cell line was assessed. HDAC1, 2 and 3 mRNA and protein were constitutively expressed in the human endometrium. High inter-individual fluctuations particularly with the endometrial HDAC1-mRNA and protein expression was found, which could be functionally and possibly clinically relevant. HDAC1 and 3 proteins were constitutively expressed in endometrial cells. The nuclei of epithelial, stromal, smooth muscle cells and in gland cells of the stratum basale and the stratum functionale were HDAC1 and 3 positive. The nuclei of cells located within lymph-follicles in the stratum basale expressed HDAC1 and HDAC3 proteins. In the endometrial blood vessels a part of the endothelial cells and a part of the smooth muscle cells of the tunica media of the arteries and the arterioles were HDAC1 and 3 protein positive. A comparison of the endometrial HDAC1 and 3 expression with the already published expression pattern of steroid hormone receptors, of steroid hormone receptor cofactors and of the proliferation marker Ki67 in the human cyclic endometrium showed that HDAC1 and 3 protein as well as these cofactors are a basic equipment of endometrial cells. HDAC1-positive cells and the proliferation marker Ki67 did not correlate. HDAC1 protein was expressed in endometrioid adenocarcinomas. HDAC1 was expressed in the tumor cells, in the stromal cells of the tumor and in infiltrating immune cells. The staining of the endometrial tumor cells was very heterogeneous. The carcinomas showed strong differences concerning the number of expressed cells and the strength of the HDAC1 protein expression (from - to +++). HDAC1 protein was detected in morphologically healthy appearing tissue, which bordered on breast carcinomas. The nuclei of epithelial and stromal cells, adipocytes, endothelial cells and the smooth muscle cells of the tunica media of the blood vessels as well as the tumor cells themselves were HDAC1 positive. According to the endometrial carcinomas, a comparison of the HDAC1 staining intensity of the examined breast carcinomas resulted in a differently strong HDAC1-expression in differently breast carcinomas. In some tumors the tumor cells differ according to the HDAC1 staining intensity (of - to +++). Negative and strongly positive tumor cells were in close neighbourhood. The HDAC1 is expressed in the T47D-cell line. The expression was not subject to a hormonal regularization. An examination of 200 breast carcinomas, which were analyzed in co-operation with the pathology and gynaecology of the University of Münster, showed that the HDAC1 protein possesses a positively prognostic marker function and represents a differentiation marker. From the tumor-specific HDAC1 expression strength as well as the specific HDAC1 expression pattern in the examined endometrial and breast carcinomas follows that a different response of the respective tumors on HDAC inhibitors is to be expected. This is to be considered with a therapy with HDAC inhibitors, since by it therapy-success can be affected.","abstract_html":"Histone deacetylases (HDACs) deacetylate lysine residues of histone proteins. Thus the connection of the DNA to the histone octamer is strengthened, whereby gene expression is restrained. HDACs are involved in steroid-hormone dependent gene expression and into carcinogenesis. HDAC-inhibitors induce differentiation of endometrial and malignantly transformed cells. They inhibit proliferation and induce apoptosis in tumor cells. Thus HDACs are therapeutic targets. The expression of class I HDACs, HDAC1, 2 and 3, both in the endometrium and the mammary gland and in endometrial and breast carcinomas is largely unknown. Therefore, we assessed HDAC1, 2 and 3 expression in above tissues as well as in the T47D-breast cancer cell line, in consideration of the HDAC1 due to its role in cell cycle control. A hormonal regulation of the HDAC expression in the endometrium and in the T47D cell line was analyzed. The mRNA expression status in the human cyclic endometrium was examined with semiquantitative RT-PCR for HDAC1 and 3 and with the real-time PCR for HDAC2. By the western blot method the HDAC1, 2 and 3 protein expression status was also analyzed. With immunhistochemistry the localization and the intracellular distribution of the HDAC1 and 3 protein were defined. By means of immunhistochemistry HDAC1 protein expression in endometrial and breast carcinomas and in the T47D-cell line was examined. A hormonal regulated HDAC1 expression in the T47D cell line was assessed. HDAC1, 2 and 3 mRNA and protein were constitutively expressed in the human endometrium. High inter-individual fluctuations particularly with the endometrial HDAC1-mRNA and protein expression was found, which could be functionally and possibly clinically relevant. HDAC1 and 3 proteins were constitutively expressed in endometrial cells. The nuclei of epithelial, stromal, smooth muscle cells and in gland cells of the stratum basale and the stratum functionale were HDAC1 and 3 positive. The nuclei of cells located within lymph-follicles in the stratum basale expressed HDAC1 and HDAC3 proteins. In the endometrial blood vessels a part of the endothelial cells and a part of the smooth muscle cells of the tunica media of the arteries and the arterioles were HDAC1 and 3 protein positive. A comparison of the endometrial HDAC1 and 3 expression with the already published expression pattern of steroid hormone receptors, of steroid hormone receptor cofactors and of the proliferation marker Ki67 in the human cyclic endometrium showed that HDAC1 and 3 protein as well as these cofactors are a basic equipment of endometrial cells. HDAC1-positive cells and the proliferation marker Ki67 did not correlate. HDAC1 protein was expressed in endometrioid adenocarcinomas. HDAC1 was expressed in the tumor cells, in the stromal cells of the tumor and in infiltrating immune cells. The staining of the endometrial tumor cells was very heterogeneous. The carcinomas showed strong differences concerning the number of expressed cells and the strength of the HDAC1 protein expression (from - to +++). HDAC1 protein was detected in morphologically healthy appearing tissue, which bordered on breast carcinomas. The nuclei of epithelial and stromal cells, adipocytes, endothelial cells and the smooth muscle cells of the tunica media of the blood vessels as well as the tumor cells themselves were HDAC1 positive. According to the endometrial carcinomas, a comparison of the HDAC1 staining intensity of the examined breast carcinomas resulted in a differently strong HDAC1-expression in differently breast carcinomas. In some tumors the tumor cells differ according to the HDAC1 staining intensity (of - to +++). Negative and strongly positive tumor cells were in close neighbourhood. The HDAC1 is expressed in the T47D-cell line. The expression was not subject to a hormonal regularization. An examination of 200 breast carcinomas, which were analyzed in co-operation with the pathology and gynaecology of the University of Münster, showed that the HDAC1 protein possesses a positively prognostic marker function and represents a differentiation marker. From the tumor-specific HDAC1 expression strength as well as the specific HDAC1 expression pattern in the examined endometrial and breast carcinomas follows that a different response of the respective tumors on HDAC inhibitors is to be expected. This is to be considered with a therapy with HDAC inhibitors, since by it therapy-success can be affected.","abstract_has_math":false,"creators":["Vloet, Jennifer Anne"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Krusche, Claudia Astrid"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007","date_published":"2007","updated_at":"2026-07-30T19:43:19Z","subjects":["info:eu-repo/classification/ddc/610","Gebärmutterschleimhaut","Mamma","Histon-Deacetylase","Steroidhormonrezeptor","Medizin","endometrium","breast","histone deacetylase","steroid hormone receptor"],"languages":["ger"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123825%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123825%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123825%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/62246","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Krusche, Claudia Astrid"]},{"key":"dc:creator","label":"Author","values":["Vloet, Jennifer Anne"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2007"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-18720"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/610","Gebärmutterschleimhaut","Mamma","Histon-Deacetylase","Steroidhormonrezeptor","Medizin","endometrium","breast","histone deacetylase","steroid hormone receptor"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["ger"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/62246","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123825%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Histone deacetylases (HDACs) deacetylate lysine residues of histone proteins. Thus the connection of the DNA to the histone octamer is strengthened, whereby gene expression is restrained. HDACs are involved in steroid-hormone dependent gene expression and into carcinogenesis. HDAC-inhibitors induce differentiation of endometrial and malignantly transformed cells. They inhibit proliferation and induce apoptosis in tumor cells. Thus HDACs are therapeutic targets. The expression of class I HDACs, HDAC1, 2 and 3, both in the endometrium and the mammary gland and in endometrial and breast carcinomas is largely unknown. Therefore, we assessed HDAC1, 2 and 3 expression in above tissues as well as in the T47D-breast cancer cell line, in consideration of the HDAC1 due to its role in cell cycle control. A hormonal regulation of the HDAC expression in the endometrium and in the T47D cell line was analyzed. The mRNA expression status in the human cyclic endometrium was examined with semiquantitative RT-PCR for HDAC1 and 3 and with the real-time PCR for HDAC2. By the western blot method the HDAC1, 2 and 3 protein expression status was also analyzed. With immunhistochemistry the localization and the intracellular distribution of the HDAC1 and 3 protein were defined. By means of immunhistochemistry HDAC1 protein expression in endometrial and breast carcinomas and in the T47D-cell line was examined. A hormonal regulated HDAC1 expression in the T47D cell line was assessed. HDAC1, 2 and 3 mRNA and protein were constitutively expressed in the human endometrium. High inter-individual fluctuations particularly with the endometrial HDAC1-mRNA and protein expression was found, which could be functionally and possibly clinically relevant. HDAC1 and 3 proteins were constitutively expressed in endometrial cells. The nuclei of epithelial, stromal, smooth muscle cells and in gland cells of the stratum basale and the stratum functionale were HDAC1 and 3 positive. The nuclei of cells located within lymph-follicles in the stratum basale expressed HDAC1 and HDAC3 proteins. In the endometrial blood vessels a part of the endothelial cells and a part of the smooth muscle cells of the tunica media of the arteries and the arterioles were HDAC1 and 3 protein positive. A comparison of the endometrial HDAC1 and 3 expression with the already published expression pattern of steroid hormone receptors, of steroid hormone receptor cofactors and of the proliferation marker Ki67 in the human cyclic endometrium showed that HDAC1 and 3 protein as well as these cofactors are a basic equipment of endometrial cells. HDAC1-positive cells and the proliferation marker Ki67 did not correlate. HDAC1 protein was expressed in endometrioid adenocarcinomas. HDAC1 was expressed in the tumor cells, in the stromal cells of the tumor and in infiltrating immune cells. The staining of the endometrial tumor cells was very heterogeneous. The carcinomas showed strong differences concerning the number of expressed cells and the strength of the HDAC1 protein expression (from - to +++). HDAC1 protein was detected in morphologically healthy appearing tissue, which bordered on breast carcinomas. The nuclei of epithelial and stromal cells, adipocytes, endothelial cells and the smooth muscle cells of the tunica media of the blood vessels as well as the tumor cells themselves were HDAC1 positive. According to the endometrial carcinomas, a comparison of the HDAC1 staining intensity of the examined breast carcinomas resulted in a differently strong HDAC1-expression in differently breast carcinomas. In some tumors the tumor cells differ according to the HDAC1 staining intensity (of - to +++). Negative and strongly positive tumor cells were in close neighbourhood. The HDAC1 is expressed in the T47D-cell line. The expression was not subject to a hormonal regularization. An examination of 200 breast carcinomas, which were analyzed in co-operation with the pathology and gynaecology of the University of Münster, showed that the HDAC1 protein possesses a positively prognostic marker function and represents a differentiation marker. From the tumor-specific HDAC1 expression strength as well as the specific HDAC1 expression pattern in the examined endometrial and breast carcinomas follows that a different response of the respective tumors on HDAC inhibitors is to be expected. This is to be considered with a therapy with HDAC inhibitors, since by it therapy-success can be affected."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University II, 68 S. : Ill., graph. Darst. (2007). = Aachen, Techn. Hochsch., Diss., 2007"]},{"key":"dc:title","label":"Title","values":["Studien zur Expression von Klasse-1-Histon-Deacetylasen im humanen Endometrium sowie in Endometrium- und Mamma-Karzinomen"]}]}],"canonical_facts":{"dc:contributor":["Krusche, Claudia Astrid"],"dc:coverage":["DE"],"dc:creator":["Vloet, Jennifer Anne"],"dc:date":["2007"],"dc:description":["Histone deacetylases (HDACs) deacetylate lysine residues of histone proteins. Thus the connection of the DNA to the histone octamer is strengthened, whereby gene expression is restrained. HDACs are involved in steroid-hormone dependent gene expression and into carcinogenesis. HDAC-inhibitors induce differentiation of endometrial and malignantly transformed cells. They inhibit proliferation and induce apoptosis in tumor cells. Thus HDACs are therapeutic targets. The expression of class I HDACs, HDAC1, 2 and 3, both in the endometrium and the mammary gland and in endometrial and breast carcinomas is largely unknown. Therefore, we assessed HDAC1, 2 and 3 expression in above tissues as well as in the T47D-breast cancer cell line, in consideration of the HDAC1 due to its role in cell cycle control. A hormonal regulation of the HDAC expression in the endometrium and in the T47D cell line was analyzed. The mRNA expression status in the human cyclic endometrium was examined with semiquantitative RT-PCR for HDAC1 and 3 and with the real-time PCR for HDAC2. By the western blot method the HDAC1, 2 and 3 protein expression status was also analyzed. With immunhistochemistry the localization and the intracellular distribution of the HDAC1 and 3 protein were defined. By means of immunhistochemistry HDAC1 protein expression in endometrial and breast carcinomas and in the T47D-cell line was examined. A hormonal regulated HDAC1 expression in the T47D cell line was assessed. HDAC1, 2 and 3 mRNA and protein were constitutively expressed in the human endometrium. High inter-individual fluctuations particularly with the endometrial HDAC1-mRNA and protein expression was found, which could be functionally and possibly clinically relevant. HDAC1 and 3 proteins were constitutively expressed in endometrial cells. The nuclei of epithelial, stromal, smooth muscle cells and in gland cells of the stratum basale and the stratum functionale were HDAC1 and 3 positive. The nuclei of cells located within lymph-follicles in the stratum basale expressed HDAC1 and HDAC3 proteins. In the endometrial blood vessels a part of the endothelial cells and a part of the smooth muscle cells of the tunica media of the arteries and the arterioles were HDAC1 and 3 protein positive. A comparison of the endometrial HDAC1 and 3 expression with the already published expression pattern of steroid hormone receptors, of steroid hormone receptor cofactors and of the proliferation marker Ki67 in the human cyclic endometrium showed that HDAC1 and 3 protein as well as these cofactors are a basic equipment of endometrial cells. HDAC1-positive cells and the proliferation marker Ki67 did not correlate. HDAC1 protein was expressed in endometrioid adenocarcinomas. HDAC1 was expressed in the tumor cells, in the stromal cells of the tumor and in infiltrating immune cells. The staining of the endometrial tumor cells was very heterogeneous. The carcinomas showed strong differences concerning the number of expressed cells and the strength of the HDAC1 protein expression (from - to +++). HDAC1 protein was detected in morphologically healthy appearing tissue, which bordered on breast carcinomas. The nuclei of epithelial and stromal cells, adipocytes, endothelial cells and the smooth muscle cells of the tunica media of the blood vessels as well as the tumor cells themselves were HDAC1 positive. According to the endometrial carcinomas, a comparison of the HDAC1 staining intensity of the examined breast carcinomas resulted in a differently strong HDAC1-expression in differently breast carcinomas. In some tumors the tumor cells differ according to the HDAC1 staining intensity (of - to +++). Negative and strongly positive tumor cells were in close neighbourhood. The HDAC1 is expressed in the T47D-cell line. The expression was not subject to a hormonal regularization. An examination of 200 breast carcinomas, which were analyzed in co-operation with the pathology and gynaecology of the University of Münster, showed that the HDAC1 protein possesses a positively prognostic marker function and represents a differentiation marker. From the tumor-specific HDAC1 expression strength as well as the specific HDAC1 expression pattern in the examined endometrial and breast carcinomas follows that a different response of the respective tumors on HDAC inhibitors is to be expected. This is to be considered with a therapy with HDAC inhibitors, since by it therapy-success can be affected."],"dc:identifier":["https://publications.rwth-aachen.de/record/62246","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123825%22"],"dc:language":["ger"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-18720"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University II, 68 S. : Ill., graph. Darst. (2007). = Aachen, Techn. Hochsch., Diss., 2007"],"dc:subject":["info:eu-repo/classification/ddc/610","Gebärmutterschleimhaut","Mamma","Histon-Deacetylase","Steroidhormonrezeptor","Medizin","endometrium","breast","histone deacetylase","steroid hormone receptor"],"dc:title":["Studien zur Expression von Klasse-1-Histon-Deacetylasen im humanen Endometrium sowie in Endometrium- und Mamma-Karzinomen"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:43:19Z"}