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Expression of Connexin 32 and Connexin 43 in Adenomatous Polyps and Hyperplastic Polyps

Year 2021, , 327 - 332, 05.09.2021
https://doi.org/10.26453/otjhs.796295

Abstract

Objective: Although connexins are thought to provide normally functioning gap junctions via a tumor suppressor gene, new studies point to an abnormal increase of connexins in various carcinomas and sarcomas. Therefore it was aimed to investigate the expression of connexin 43 (Cx43) and connexin 32 (Cx32) in adenomatous and hyperplastic polyps.

Materials and Methods: This retrospective study included 32 cases with adenomatous polyps and 42 cases with hyperplastic polyps, between 2014 and 2015. The samples were stained with immunohistochemical staining method with Cx43 and Cx32 and evaluated.

Results: In our study, we observed that Cx43 and Cx32 staining increased in hyperplastic polyps compared to adenomatous polyps (p=0.039, p=0.048 respectively). Statistically, there were no significant correlations between age, sex, location, and diameter with staining pattern.

Conclusion: Loss of Cx43 and Cx32 staining in adenomatous polyps was noted and thought to be related to dysplasia. 

References

  • Ruch RJ, Porter S, Koffler LD, Dwyer-Nield LD, Malkinson AM. Defective gap junctional intercellular communication in lung cancer: loss of an important mediator of tissue homeostasis and phenotypic regulation. Exp Lung Res. 2001;27(3):231-243. doi:10.1080/019021401300053984
  • Goodenough DA, Goliger JA, Paul DL. Connexins, connexons, and intercellular communication. Annu Rev Biochem. 1996;65:475-502. doi:10.1146/annurev.bi.65.070196.002355
  • Kanczuga-Koda L, Sulkowski S, Lenczewski A, et al. Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer. J Clin Pathol. 2006;59(4):429-433. doi:10.1136/jcp.2005.029272
  • Krutovskikh VA, Piccoli C, Yamasaki H. Gap junction intercellular communication propagates cell death in cancerous cells. Oncogene. 2002;21(13):1989-1999. doi:10.1038/sj.onc.1205187
  • Scemes E, Suadicani SO, Dahl G, Spray DC. Connexin and pannexin mediated cell-cell communication. Neuron Glia Biol. 2007;3(3):199-208. doi:10.1017/S1740925X08000069
  • Beyer EC, Davis LM, Saffitz JE, Veenstra RD. Cardiac intercellular communication: consequences of connexin distribution and diversity. Braz J Med Biol Res. 1995;28(4):415-425.
  • Mulkearns-Hubert EE, Reizes O, Lathia JD. Connexins in Cancer: Jekyll or Hyde? Biomolecules. 2020;10;10(12):1654. doi:10.3390/biom10121654
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021. doi:10.3322/caac.21660
  • Poyet C, Buser L, Roudnicky F, et al. Connexin 43 expression predicts poor progression-free survival in patients with non-muscle invasive urothelial bladder cancer. J Clin Pathol. 2015;68(10):819-824. doi:10.1136/jclinpath-2015-202898
  • el-Sabban ME, Pauli BU. Adhesion-mediated gap junctional communication between lung-metastatatic cancer cells and endothelium. Invasion Metastasis. 1994-1995;14(1-6):164-176.
  • Han Y, Zhang PJ, Chen T, Yum SW, Pasha T, Furth EE. Connexin43 Expression increases in the epithelium and stroma along the colonic neoplastic progression pathway: Implications for its oncogenic role. Gastroenterol Res Pract. 2011;2011:561719. doi:10.1155/2011/561719
  • Aasen T, Leithe E, Graham SV, Kameritsch P, Mayán MD, Mesnil M, Pogoda K, Tabernero A. Connexins in cancer: bridging the gap to the clinic. Oncogene. 2019 Jun;38(23):4429-4451. doi:10.1038/s41388-019-0741-6
  • Sheen IS, Jeng KS, Wang PC, et al. Are gap junction gene connexins 26, 32 and 43 of prognostic values in hepatocellular carcinoma? A prospective study. World J Gastroenterol. 2004;10(19):2785-2790. doi:10.3748/wjg.v10.i19.2785
  • Elzarrad MK, Haroon A, Willecke K, Dobrowolski R, Gillespie MN, Al-Mehdi AB. Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium. BMC Med. 2008;6:20. doi:10.1186/1741-7015-6-20
  • Dubina MV, Iatckii NA, Popov DE, Vasil'ev SV, Krutovskikh VA. Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancer. Oncogene. 2002;21(32):4992-4996. doi:10.1038/sj.onc.1205630
  • Cottrell S, Bicknell D, Kaklamanis L, Bodmer WF. Molecular analysis of APC mutations in familial adenomatous polyposis and sporadic colon carcinomas. Lancet. 1992;340(8820):626-630. doi:10.1016/0140-6736(92)92169-g
  • Sparks AB, Morin PJ, Vogelstein B, Kinzler KW. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res. 1998;58(6):1130-1134.
  • Otori K, Konishi M, Sugiyama K, et al. Infrequent somatic mutation of the adenomatous polyposis coli gene in aberrant crypt foci of human colon tissue. Cancer. 1998;83(5):896-900. doi:10.1002/(sici)1097-0142(19980901)83
  • van der Heyden MA, Rook MB, Hermans MM, et al. Identification of connexin43 as a functional target for Wnt signalling. J Cell Sci. 1998;111(12):1741-1749.
  • Husøy T, Knutsen HK, Cruciani V, et al. Connexin43 is overexpressed in Apc (Min/+)-mice adenomas and colocalises with COX-2 in myofibroblasts. Int J Cancer. 2005;116(3):351-358. doi:10.1002/ijc.21025
  • Araki Y, Okamura S, Hussain SP, et al. Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways. Cancer Res. 2003;63(3):728-734.
  • Shtutman M, Zhurinsky J, Simcha I, et al. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA. 1999;96(10):5522-5527. doi:10.1073/pnas. 96. 10.5522
  • Morin PJ. Beta-catenin signaling and cancer. Bioessays. 1999;21(12):1021-30. doi:10.1002/(SICI)1521-1878(199912)22:1<1021::AID-BIES6>3.0.CO;2-P
  • Hieber AD, King TJ, Morioka S, Fukushima LH, Franke AA, Bertram JS. Comparative effects of all-trans beta-carotene vs. 9-cis beta-carotene on carcinogen-induced neoplastic transformation and connexin 43 expression in murine 10T1/2 cells and on the differentiation of human keratinocytes. Nutr. Cancer. 2000;37:234-244.
  • King TJ, Fukushima LH, Hieber AD, Shimabukuro KA, Sakr WA, Bertram JS. Reduced levels of connexin 43 in cervical dysplasia: inducible expression in a cervical carcinoma cell line decreases neoplastic potential with implications for tumor progression. Carcinogenesis. 2000;(21)6:1097-1109.
  • Bertram JS. Dietary carotenoids, connexins and cancer: what is the connection? Biochem Soc Trans. 2004;32(Pt-6):985-989. doi:10.1042/BST0320985
  • Puzzo L, Caltabiano R, Parenti R, Trapasso S, Allegra E. Connexin 43 (Cx43) expression in laryngeal squamous cell carcinomas: Preliminary data on its possible prognostic role. Head Neck Pathol. 2016;10(3):292-297. doi:10.1007/s12105-016-0685-x
  • Wilgenbus KK, Kirkpatrick CJ, Knuechel R, Willecke K, Traub O. Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues. Int J Cancer. 1992;51(4):522-529. doi:10.1002/ijc.291051040
  • Dános K, Brauswetter D, Birtalan E, et al. The Potential prognostic value of connexin 43 expression in head and neck squamous cell carcinomas. Appl Immunohistochem Mol Morphol. 2016;24(7):476-481. doi:10.1097/PAI.0000000000000212

Adenomatöz ve Hiperplastik Poliplerde Konneksin 32 ve Konneksin 43 Ekspresyonu

Year 2021, , 327 - 332, 05.09.2021
https://doi.org/10.26453/otjhs.796295

Abstract

Amaç: Konneksinlerin tümör baskılayıcı bir gen yoluyla normal işleyen geçit bağlantıları sağladığı düşünülse de yeni çalışmalar çeşitli karsinom ve sarkomlarda konneksinlerin anormal artışına işaret etmektedir. Bu nedenle adenomatöz ve hiperplastik poliplerde connexin 43 (Cx43) ve connexin 32 (Cx32) ekspresyonunun araştırılması amaçlandı.

Materyal ve Metot: Bu retrospektif çalışmaya 2014-2015 yılları arasında adenomatöz polipli 32 olgu ve hiperplastik polipli 42 olgu dahil edildi. Örnekler Cx43 ve Cx32 ile immünohistokimyasal boyama yöntemi ile boyandı ve değerlendirildi.

Bulgular: Çalışmamızda, hiperplastik poliplerde adenomatöz poliplere göre Cx43 ve Cx32 boyanmalarının arttığını gözlemledik (sırasıyla p=0,039, p=0,048). İstatistiksel olarak yaş, cinsiyet, yerleşim yeri ve çap ile boyama paterni arasında anlamlı bir ilişki yoktu.

Sonuç: Adenomatöz poliplerde Cx43 ve Cx32 boyanmasının azaldığı ve bu durumun displazi ile ilişkili olduğu düşünüldü. 

References

  • Ruch RJ, Porter S, Koffler LD, Dwyer-Nield LD, Malkinson AM. Defective gap junctional intercellular communication in lung cancer: loss of an important mediator of tissue homeostasis and phenotypic regulation. Exp Lung Res. 2001;27(3):231-243. doi:10.1080/019021401300053984
  • Goodenough DA, Goliger JA, Paul DL. Connexins, connexons, and intercellular communication. Annu Rev Biochem. 1996;65:475-502. doi:10.1146/annurev.bi.65.070196.002355
  • Kanczuga-Koda L, Sulkowski S, Lenczewski A, et al. Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer. J Clin Pathol. 2006;59(4):429-433. doi:10.1136/jcp.2005.029272
  • Krutovskikh VA, Piccoli C, Yamasaki H. Gap junction intercellular communication propagates cell death in cancerous cells. Oncogene. 2002;21(13):1989-1999. doi:10.1038/sj.onc.1205187
  • Scemes E, Suadicani SO, Dahl G, Spray DC. Connexin and pannexin mediated cell-cell communication. Neuron Glia Biol. 2007;3(3):199-208. doi:10.1017/S1740925X08000069
  • Beyer EC, Davis LM, Saffitz JE, Veenstra RD. Cardiac intercellular communication: consequences of connexin distribution and diversity. Braz J Med Biol Res. 1995;28(4):415-425.
  • Mulkearns-Hubert EE, Reizes O, Lathia JD. Connexins in Cancer: Jekyll or Hyde? Biomolecules. 2020;10;10(12):1654. doi:10.3390/biom10121654
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021. doi:10.3322/caac.21660
  • Poyet C, Buser L, Roudnicky F, et al. Connexin 43 expression predicts poor progression-free survival in patients with non-muscle invasive urothelial bladder cancer. J Clin Pathol. 2015;68(10):819-824. doi:10.1136/jclinpath-2015-202898
  • el-Sabban ME, Pauli BU. Adhesion-mediated gap junctional communication between lung-metastatatic cancer cells and endothelium. Invasion Metastasis. 1994-1995;14(1-6):164-176.
  • Han Y, Zhang PJ, Chen T, Yum SW, Pasha T, Furth EE. Connexin43 Expression increases in the epithelium and stroma along the colonic neoplastic progression pathway: Implications for its oncogenic role. Gastroenterol Res Pract. 2011;2011:561719. doi:10.1155/2011/561719
  • Aasen T, Leithe E, Graham SV, Kameritsch P, Mayán MD, Mesnil M, Pogoda K, Tabernero A. Connexins in cancer: bridging the gap to the clinic. Oncogene. 2019 Jun;38(23):4429-4451. doi:10.1038/s41388-019-0741-6
  • Sheen IS, Jeng KS, Wang PC, et al. Are gap junction gene connexins 26, 32 and 43 of prognostic values in hepatocellular carcinoma? A prospective study. World J Gastroenterol. 2004;10(19):2785-2790. doi:10.3748/wjg.v10.i19.2785
  • Elzarrad MK, Haroon A, Willecke K, Dobrowolski R, Gillespie MN, Al-Mehdi AB. Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium. BMC Med. 2008;6:20. doi:10.1186/1741-7015-6-20
  • Dubina MV, Iatckii NA, Popov DE, Vasil'ev SV, Krutovskikh VA. Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancer. Oncogene. 2002;21(32):4992-4996. doi:10.1038/sj.onc.1205630
  • Cottrell S, Bicknell D, Kaklamanis L, Bodmer WF. Molecular analysis of APC mutations in familial adenomatous polyposis and sporadic colon carcinomas. Lancet. 1992;340(8820):626-630. doi:10.1016/0140-6736(92)92169-g
  • Sparks AB, Morin PJ, Vogelstein B, Kinzler KW. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res. 1998;58(6):1130-1134.
  • Otori K, Konishi M, Sugiyama K, et al. Infrequent somatic mutation of the adenomatous polyposis coli gene in aberrant crypt foci of human colon tissue. Cancer. 1998;83(5):896-900. doi:10.1002/(sici)1097-0142(19980901)83
  • van der Heyden MA, Rook MB, Hermans MM, et al. Identification of connexin43 as a functional target for Wnt signalling. J Cell Sci. 1998;111(12):1741-1749.
  • Husøy T, Knutsen HK, Cruciani V, et al. Connexin43 is overexpressed in Apc (Min/+)-mice adenomas and colocalises with COX-2 in myofibroblasts. Int J Cancer. 2005;116(3):351-358. doi:10.1002/ijc.21025
  • Araki Y, Okamura S, Hussain SP, et al. Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways. Cancer Res. 2003;63(3):728-734.
  • Shtutman M, Zhurinsky J, Simcha I, et al. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA. 1999;96(10):5522-5527. doi:10.1073/pnas. 96. 10.5522
  • Morin PJ. Beta-catenin signaling and cancer. Bioessays. 1999;21(12):1021-30. doi:10.1002/(SICI)1521-1878(199912)22:1<1021::AID-BIES6>3.0.CO;2-P
  • Hieber AD, King TJ, Morioka S, Fukushima LH, Franke AA, Bertram JS. Comparative effects of all-trans beta-carotene vs. 9-cis beta-carotene on carcinogen-induced neoplastic transformation and connexin 43 expression in murine 10T1/2 cells and on the differentiation of human keratinocytes. Nutr. Cancer. 2000;37:234-244.
  • King TJ, Fukushima LH, Hieber AD, Shimabukuro KA, Sakr WA, Bertram JS. Reduced levels of connexin 43 in cervical dysplasia: inducible expression in a cervical carcinoma cell line decreases neoplastic potential with implications for tumor progression. Carcinogenesis. 2000;(21)6:1097-1109.
  • Bertram JS. Dietary carotenoids, connexins and cancer: what is the connection? Biochem Soc Trans. 2004;32(Pt-6):985-989. doi:10.1042/BST0320985
  • Puzzo L, Caltabiano R, Parenti R, Trapasso S, Allegra E. Connexin 43 (Cx43) expression in laryngeal squamous cell carcinomas: Preliminary data on its possible prognostic role. Head Neck Pathol. 2016;10(3):292-297. doi:10.1007/s12105-016-0685-x
  • Wilgenbus KK, Kirkpatrick CJ, Knuechel R, Willecke K, Traub O. Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues. Int J Cancer. 1992;51(4):522-529. doi:10.1002/ijc.291051040
  • Dános K, Brauswetter D, Birtalan E, et al. The Potential prognostic value of connexin 43 expression in head and neck squamous cell carcinomas. Appl Immunohistochem Mol Morphol. 2016;24(7):476-481. doi:10.1097/PAI.0000000000000212
There are 29 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research article
Authors

Havva Erdem 0000-0002-3074-0240

Ali Aslan 0000-0002-9674-5618

Soner Çankaya 0000-0001-8056-1892

Zeynep Doğangüzel This is me 0000-0001-8809-9225

Publication Date September 5, 2021
Submission Date December 20, 2020
Acceptance Date June 28, 2021
Published in Issue Year 2021

Cite

AMA Erdem H, Aslan A, Çankaya S, Doğangüzel Z. Expression of Connexin 32 and Connexin 43 in Adenomatous Polyps and Hyperplastic Polyps. OTSBD. September 2021;6(3):327-332. doi:10.26453/otjhs.796295

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