Skip to main content
Top
Published in: Cancer Cell International 1/2013

Open Access 01-12-2013 | Primary research

Expression patterns of Phf5a/PHF5A and Gja1/GJA1 in rat and human endometrial cancer

Authors: Eva Falck, Karin Klinga-Levan

Published in: Cancer Cell International | Issue 1/2013

Login to get access

Abstract

Endometrial adenocarcinoma is the most frequently diagnosed cancer of the female genital tract in the western world. Studies of complex diseases can be difficult to perform on human tumor samples due to the high genetic heterogeneity in human. The use of rat models is preferable since rat has similarities in pathogenesis and histopathological properties to that of human.
A genomic region including the highly conserved Phf5a gene associated to development of EAC has previously been identified in an association study. PHF5A has been suggested to acts as a transcription factor or cofactor in the up regulation of expression of Gja1 gene in the presence of estrogen. It has earlier been shown that the Phf5a gene is down regulated in rat EAC derived cell lines by means of expression microarrays.
We analyzed the expression of Phf5a and Gja1 by qPCR, and potential relations between the two genes in EAC tumors and non-malignant cell lines derived from the BDII rat model. In addition, the expression pattern of these genes was compared in rat and human EAC tumor samples.
Changes in expression for Phf5a/PHF5A were found in tumors from both rat and human even though the observed pattern was not completely consistent between the two species. By separating rat EAC cell lines according to the genetic background, a significant lower expression of Phf5a in one of the two cross backgrounds was revealed, but not for the other. In contrast to other studies, Phf5a/PHF5A regulation of Gja1/GJA1 was not revealed in this study.
Appendix
Available only for authorised users
Literature
1.
go back to reference Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I: Endometrial cancer. Lancet. 2005, 366 (9484): 491-505. 10.1016/S0140-6736(05)67063-8.CrossRefPubMed Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I: Endometrial cancer. Lancet. 2005, 366 (9484): 491-505. 10.1016/S0140-6736(05)67063-8.CrossRefPubMed
2.
go back to reference Vollmer G: Endometrial cancer: experimental models useful for studies on molecular aspects of endometrial cancer and carcinogenesis. Endocr Relat Cancer. 2003, 10 (1): 23-42. 10.1677/erc.0.0100023.CrossRefPubMed Vollmer G: Endometrial cancer: experimental models useful for studies on molecular aspects of endometrial cancer and carcinogenesis. Endocr Relat Cancer. 2003, 10 (1): 23-42. 10.1677/erc.0.0100023.CrossRefPubMed
3.
go back to reference Cavanagh D, Fiorica JV, Hoffman MS, Durfee J, Nicosia SV: Adenocarcinoma of the endometrium: an institutional review. Cancer Control. 1999, 6 (4): 354-360.PubMed Cavanagh D, Fiorica JV, Hoffman MS, Durfee J, Nicosia SV: Adenocarcinoma of the endometrium: an institutional review. Cancer Control. 1999, 6 (4): 354-360.PubMed
4.
go back to reference Samuelson E, Hedberg C, Nilsson S, Behboudi A: Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats. Endocr Relat Cancer. 2009, 16 (1): 99-111.CrossRefPubMed Samuelson E, Hedberg C, Nilsson S, Behboudi A: Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats. Endocr Relat Cancer. 2009, 16 (1): 99-111.CrossRefPubMed
5.
go back to reference Deerberg F, Kaspareit J: Endometrial carcinoma in BD II/Han rats: model of a spontaneous hormone-dependent tumor. J Natl Cancer Inst. 1987, 78 (6): 1245-1251.PubMed Deerberg F, Kaspareit J: Endometrial carcinoma in BD II/Han rats: model of a spontaneous hormone-dependent tumor. J Natl Cancer Inst. 1987, 78 (6): 1245-1251.PubMed
6.
go back to reference Roshani L, Beckman B, Szpirer S, Hedrich HJ, Klinga-Levan K: The rat as a model for identification of susceptibilty genes involved in the development of endometrial carcinoma. Rat Genome. 2000, 6: 76- Roshani L, Beckman B, Szpirer S, Hedrich HJ, Klinga-Levan K: The rat as a model for identification of susceptibilty genes involved in the development of endometrial carcinoma. Rat Genome. 2000, 6: 76-
7.
go back to reference Roshani L, Mallon P, Sjostrand E, Wedekind D, Szpirer J, Szpirer C, Hedrich HJ, Klinga-Levan K: Genetic analysis of susceptibility to endometrial adenocarcinoma in the BDII rat model. Cancer Genet Cytogenet. 2005, 158 (2): 137-141. 10.1016/j.cancergencyto.2004.08.034.CrossRefPubMed Roshani L, Mallon P, Sjostrand E, Wedekind D, Szpirer J, Szpirer C, Hedrich HJ, Klinga-Levan K: Genetic analysis of susceptibility to endometrial adenocarcinoma in the BDII rat model. Cancer Genet Cytogenet. 2005, 158 (2): 137-141. 10.1016/j.cancergencyto.2004.08.034.CrossRefPubMed
8.
go back to reference Karlsson S, Olsson B, Klinga-Levan K: Gene expression profiling predicts a three-gene expression signature of endometrial adenocarcinoma in a rat model. Cancer Cell Int. 2009, 9: 12-10.1186/1475-2867-9-12.PubMedCentralCrossRefPubMed Karlsson S, Olsson B, Klinga-Levan K: Gene expression profiling predicts a three-gene expression signature of endometrial adenocarcinoma in a rat model. Cancer Cell Int. 2009, 9: 12-10.1186/1475-2867-9-12.PubMedCentralCrossRefPubMed
9.
go back to reference Trappe R, Ahmed M, Glaser B, Vogel C, Tascou S, Burfeind P, Engel W: Identification and characterization of a novel murine multigene family containing a PHD-finger-like motif. Biochem Biophys Res Commun. 2002, 293 (2): 816-826. 10.1016/S0006-291X(02)00277-2.CrossRefPubMed Trappe R, Ahmed M, Glaser B, Vogel C, Tascou S, Burfeind P, Engel W: Identification and characterization of a novel murine multigene family containing a PHD-finger-like motif. Biochem Biophys Res Commun. 2002, 293 (2): 816-826. 10.1016/S0006-291X(02)00277-2.CrossRefPubMed
10.
go back to reference Oltra E, Fulvia V, Werner R, D’Urso G: A novel RING-finger-like protein Ini1 is essential for cell cycle progression in fission yeast. J Cell Sci. 2003, 117: 967-974.CrossRef Oltra E, Fulvia V, Werner R, D’Urso G: A novel RING-finger-like protein Ini1 is essential for cell cycle progression in fission yeast. J Cell Sci. 2003, 117: 967-974.CrossRef
11.
go back to reference Oltra E, Pfeifer I, Werner R: Ini, a small nuclear protein that enhances the response of the connexin43 gene to estrogen. Endocrinology. 2003, 144 (7): 3148-3158. 10.1210/en.2002-0176.CrossRefPubMed Oltra E, Pfeifer I, Werner R: Ini, a small nuclear protein that enhances the response of the connexin43 gene to estrogen. Endocrinology. 2003, 144 (7): 3148-3158. 10.1210/en.2002-0176.CrossRefPubMed
12.
go back to reference Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC: Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev. 2003, 83 (4): 1359-1400.CrossRefPubMed Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC: Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev. 2003, 83 (4): 1359-1400.CrossRefPubMed
13.
go back to reference Sohl G, Willecke K: An update on connexin genes and their nomenclature in mouse and man. Cell Commun Adhes. 2003, 10 (4–6): 173-180.CrossRefPubMed Sohl G, Willecke K: An update on connexin genes and their nomenclature in mouse and man. Cell Commun Adhes. 2003, 10 (4–6): 173-180.CrossRefPubMed
14.
go back to reference Sirnes S, Bruun J, Kolberg M, Kjenseth A, Lind GE, Svindland A, Brech A, Nesbakken A, Lothe RA, Leithe E, Rivedal E: Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. Int J Cancer. 2012, 131 (3): 570-581. 10.1002/ijc.26392.CrossRefPubMed Sirnes S, Bruun J, Kolberg M, Kjenseth A, Lind GE, Svindland A, Brech A, Nesbakken A, Lothe RA, Leithe E, Rivedal E: Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. Int J Cancer. 2012, 131 (3): 570-581. 10.1002/ijc.26392.CrossRefPubMed
15.
go back to reference Vinken M, Vanhaecke T, Papeleu P, Snykers S, Henkens T, Rogiers V: Connexins and their channels in cell growth and cell death. Cell Signal. 2006, 18 (5): 592-600. 10.1016/j.cellsig.2005.08.012.CrossRefPubMed Vinken M, Vanhaecke T, Papeleu P, Snykers S, Henkens T, Rogiers V: Connexins and their channels in cell growth and cell death. Cell Signal. 2006, 18 (5): 592-600. 10.1016/j.cellsig.2005.08.012.CrossRefPubMed
16.
go back to reference Leithe E, Sirnes S, Omori Y, Rivedal E: Downregulation of gap junctions in cancer cells. Crit Rev Oncog. 2006, 12 (3–4): 225-256.CrossRefPubMed Leithe E, Sirnes S, Omori Y, Rivedal E: Downregulation of gap junctions in cancer cells. Crit Rev Oncog. 2006, 12 (3–4): 225-256.CrossRefPubMed
17.
go back to reference McLachlan E, Shao Q, Wang HL, Langlois S, Laird DW: Connexins act as tumor suppressors in three-dimensional mammary cell organoids by regulating differentiation and angiogenesis. Cancer Res. 2006, 66 (20): 9886-9894. 10.1158/0008-5472.CAN-05-4302.CrossRefPubMed McLachlan E, Shao Q, Wang HL, Langlois S, Laird DW: Connexins act as tumor suppressors in three-dimensional mammary cell organoids by regulating differentiation and angiogenesis. Cancer Res. 2006, 66 (20): 9886-9894. 10.1158/0008-5472.CAN-05-4302.CrossRefPubMed
18.
go back to reference Schlemmer SR, Novotny DB, Kaufman DG: Changes in connexin 43 protein expression in human endometrial carcinoma. Exp Mol Pathol. 1999, 67 (3): 150-163. 10.1006/exmp.1999.2286.CrossRefPubMed Schlemmer SR, Novotny DB, Kaufman DG: Changes in connexin 43 protein expression in human endometrial carcinoma. Exp Mol Pathol. 1999, 67 (3): 150-163. 10.1006/exmp.1999.2286.CrossRefPubMed
19.
go back to reference Trappe R, Schulze E, Rzymski T, Frode S, Engel W: The Caenorhabditis elegans ortholog of human PHF5a shows a muscle-specific expression domain and is essential for C. elegans morphogenetic development. Biochem Biophys Res Commun. 2002, 297 (4): 1049-1057. 10.1016/S0006-291X(02)02276-3.CrossRefPubMed Trappe R, Schulze E, Rzymski T, Frode S, Engel W: The Caenorhabditis elegans ortholog of human PHF5a shows a muscle-specific expression domain and is essential for C. elegans morphogenetic development. Biochem Biophys Res Commun. 2002, 297 (4): 1049-1057. 10.1016/S0006-291X(02)02276-3.CrossRefPubMed
20.
go back to reference Piechocki MP, Burk RD, Ruch RJ: Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat liver cells. Carcinogenesis. 1999, 20 (3): 401-406. 10.1093/carcin/20.3.401.CrossRefPubMed Piechocki MP, Burk RD, Ruch RJ: Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat liver cells. Carcinogenesis. 1999, 20 (3): 401-406. 10.1093/carcin/20.3.401.CrossRefPubMed
21.
go back to reference Sirnes S, Honne H, Ahmed D, Danielsen SA, Rognum TO, Meling GI, Leithe E, Rivedal E, Lothe RA, Lind GE: DNA methylation analyses of the connexin gene family reveal silencing of GJC1 (Connexin45) by promoter hypermethylation in colorectal cancer. Epigenetics. 2011, 6 (5): 602-609. 10.4161/epi.6.5.15237.CrossRefPubMed Sirnes S, Honne H, Ahmed D, Danielsen SA, Rognum TO, Meling GI, Leithe E, Rivedal E, Lothe RA, Lind GE: DNA methylation analyses of the connexin gene family reveal silencing of GJC1 (Connexin45) by promoter hypermethylation in colorectal cancer. Epigenetics. 2011, 6 (5): 602-609. 10.4161/epi.6.5.15237.CrossRefPubMed
22.
go back to reference Kirchhoff T, Gaudet MM, Antoniou AC, McGuffog L, Humphreys MK, Dunning AM, Bojesen SE, Nordestgaard BG, Flyger H, Kang D, Yoo KY, Noh DY, Ahn SH, Dork T, Schurmann P, Karstens JH, Hillemanns P, Couch FJ, Olson J, Vachon C, Wang X, Cox A, Brock I, Elliott G, Reed MW, Burwinkel B, Meindl A, Brauch H, Hamann U, Ko YD: Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2. PLoS One. 2012, 7 (6): e35706-10.1371/journal.pone.0035706.PubMedCentralCrossRefPubMed Kirchhoff T, Gaudet MM, Antoniou AC, McGuffog L, Humphreys MK, Dunning AM, Bojesen SE, Nordestgaard BG, Flyger H, Kang D, Yoo KY, Noh DY, Ahn SH, Dork T, Schurmann P, Karstens JH, Hillemanns P, Couch FJ, Olson J, Vachon C, Wang X, Cox A, Brock I, Elliott G, Reed MW, Burwinkel B, Meindl A, Brauch H, Hamann U, Ko YD: Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2. PLoS One. 2012, 7 (6): e35706-10.1371/journal.pone.0035706.PubMedCentralCrossRefPubMed
23.
go back to reference Wang X, Pankratz VS, Fredericksen Z, Tarrell R, Karaus M, McGuffog L, Pharaoh PD, Ponder BA, Dunning AM, Peock S, Cook M, Oliver C, Frost D, Sinilnikova OM, Stoppa-Lyonnet D, Mazoyer S, Houdayer C, Hogervorst FB, Hooning MJ, Ligtenberg MJ, Spurdle A, Chenevix-Trench G, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Domchek SM, Nathanson KL, Rebbeck TR, Singer CF: Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Hum Mol Genet. 2010, 19 (14): 2886-2897. 10.1093/hmg/ddq174.PubMedCentralCrossRefPubMed Wang X, Pankratz VS, Fredericksen Z, Tarrell R, Karaus M, McGuffog L, Pharaoh PD, Ponder BA, Dunning AM, Peock S, Cook M, Oliver C, Frost D, Sinilnikova OM, Stoppa-Lyonnet D, Mazoyer S, Houdayer C, Hogervorst FB, Hooning MJ, Ligtenberg MJ, Spurdle A, Chenevix-Trench G, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Domchek SM, Nathanson KL, Rebbeck TR, Singer CF: Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Hum Mol Genet. 2010, 19 (14): 2886-2897. 10.1093/hmg/ddq174.PubMedCentralCrossRefPubMed
24.
go back to reference Roshani L, Wedekind D, Szpirer J, Taib Z, Szpirer C, Beckman B, Rivière M, Hedrich HJ, Klinga-Levan K: Genetic identification of multiple susceptibility genes involved in the development of endometrial carcinoma in a rat model. Int J Cancer. 2001, 94 (6): 795-799. 10.1002/ijc.1553.CrossRefPubMed Roshani L, Wedekind D, Szpirer J, Taib Z, Szpirer C, Beckman B, Rivière M, Hedrich HJ, Klinga-Levan K: Genetic identification of multiple susceptibility genes involved in the development of endometrial carcinoma in a rat model. Int J Cancer. 2001, 94 (6): 795-799. 10.1002/ijc.1553.CrossRefPubMed
25.
go back to reference Falck E, Behboudi A, Klinga-Levan K: The impact of the genetic background on the genome make-up of tumor cells. Genes Chromosomes Cancer. 2012, 51 (5): 438-446. 10.1002/gcc.21929.CrossRefPubMed Falck E, Behboudi A, Klinga-Levan K: The impact of the genetic background on the genome make-up of tumor cells. Genes Chromosomes Cancer. 2012, 51 (5): 438-446. 10.1002/gcc.21929.CrossRefPubMed
26.
go back to reference Laird DW, Fistouris P, Batist G, Alpert L, Huynh HT, Carystinos GD, Alaoui-Jamali MA: Deficiency of connexin43 gap junctions is an independent marker for breast tumors. Cancer Res. 1999, 59 (16): 4104-4110.PubMed Laird DW, Fistouris P, Batist G, Alpert L, Huynh HT, Carystinos GD, Alaoui-Jamali MA: Deficiency of connexin43 gap junctions is an independent marker for breast tumors. Cancer Res. 1999, 59 (16): 4104-4110.PubMed
27.
go back to reference Chen JT, Cheng YW, Chou MC, Sen-Lin T, Lai WW, Ho WL, Lee H: The correlation between aberrant connexin 43 mRNA expression induced by promoter methylation and nodal micrometastasis in non-small cell lung cancer. Clin Cancer Res. 2003, 9 (11): 4200-4204.PubMed Chen JT, Cheng YW, Chou MC, Sen-Lin T, Lai WW, Ho WL, Lee H: The correlation between aberrant connexin 43 mRNA expression induced by promoter methylation and nodal micrometastasis in non-small cell lung cancer. Clin Cancer Res. 2003, 9 (11): 4200-4204.PubMed
28.
go back to reference Saito T, Nishimura M, Kudo R, Yamasaki H: Suppressed gap junctional intercellular communication in carcinogenesis of endometrium. Int J Cancer. 2001, 93 (3): 317-323. 10.1002/ijc.1350.CrossRefPubMed Saito T, Nishimura M, Kudo R, Yamasaki H: Suppressed gap junctional intercellular communication in carcinogenesis of endometrium. Int J Cancer. 2001, 93 (3): 317-323. 10.1002/ijc.1350.CrossRefPubMed
29.
go back to reference Lesniewicz T, Kanczuga-Koda L, Baltaziak M, Jarzabek K, Rutkowski R, Koda M, Wincewicz A, Sulkowska M, Sulkowski S: Comparative evaluation of estrogen and progesterone receptor expression with connexins 26 and 43 in endometrial cancer. Int J Gynecol Cancer. 2009, 19 (7): 1253-1257. 10.1111/IGC.0b013e3181a40618.CrossRefPubMed Lesniewicz T, Kanczuga-Koda L, Baltaziak M, Jarzabek K, Rutkowski R, Koda M, Wincewicz A, Sulkowska M, Sulkowski S: Comparative evaluation of estrogen and progesterone receptor expression with connexins 26 and 43 in endometrial cancer. Int J Gynecol Cancer. 2009, 19 (7): 1253-1257. 10.1111/IGC.0b013e3181a40618.CrossRefPubMed
30.
go back to reference Karlsson S, Klinga-Levan K: Expression analysis of human endometrial adenocarcinoma in an inbred rat model. Adv Exp Med Biol. 2008, 617: 503-509. 10.1007/978-0-387-69080-3_50.CrossRefPubMed Karlsson S, Klinga-Levan K: Expression analysis of human endometrial adenocarcinoma in an inbred rat model. Adv Exp Med Biol. 2008, 617: 503-509. 10.1007/978-0-387-69080-3_50.CrossRefPubMed
31.
go back to reference Falck E, Karlsson S, Carlsson J, Helenius G, Karlsson M, Klinga-Levan K: Loss of glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma. Cancer Cell Int. 2010, 10: 46-10.1186/1475-2867-10-46.PubMedCentralCrossRefPubMed Falck E, Karlsson S, Carlsson J, Helenius G, Karlsson M, Klinga-Levan K: Loss of glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma. Cancer Cell Int. 2010, 10: 46-10.1186/1475-2867-10-46.PubMedCentralCrossRefPubMed
Metadata
Title
Expression patterns of Phf5a/PHF5A and Gja1/GJA1 in rat and human endometrial cancer
Authors
Eva Falck
Karin Klinga-Levan
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2013
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-13-43

Other articles of this Issue 1/2013

Cancer Cell International 1/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine