Study on the expression of testin in the testes of dogs

Ciaputa, Rafał; Nowak, Marcin; Dzimira, Stanisław; Brambilla, Eleonora; Kandefer-Gola, Małgorzata; Tomaszek, Alicja; Popiel-Kopaczyk, Aneta; Dzięgiel, Piotr; Grieco, Valeria

doi:10.2478/jvetres-2023-0055

Abstract

Introduction

Testin is a protein involved in cell mobility, adhesion and colony formation. In rats, testin presence has been reported in the testes, and its possible role in spermatogenesis has been suggested. Studies in humans also suggest a possible role of testin as a cancer suppressor protein. In the dog, which represents both an important pet species and a good animal model for studying biological and pathological testicular processes, the presence of testin has never been reported.

Material and Methods

In the present study, the expression of testin in foetal, prepubertal, adult and aged canine testes was investigated. Testes from 5 adult and 3 aged dogs, from 2 one-month-old puppies and from 2 foetuses miscarried at the end of pregnancy were immunohistochemically examined with a commercial antibody against testin.

Results

Testin was intensely expressed in Sertoli cells in every testis examined. Spermatids were also positive for testin in mature dogs and in the testicular areas of the aged ones which were not atrophic. Weak expression of testin was also detected in all testes examined.

Conclusion

The present study, the first demonstrating the presence of testin in canine testes, provides the basis for further dog–human comparative research and for studies on the role of this protein in canine physiology, reproduction and testicular pathologies.

References

Allen H.L., Newton C.D.: Animal model of human disease. Juvenile rheumatoid arthritis. Animal model: rheumatoid arthritis in the dog. Am J Pathol 1975, 81, 699–702.
Search in Google Scholar Back to article
Bardin C.W., Cheng C.Y., Musto N.A., Gunsalus G.L.: The Sertoli cell. In: The Physiology of Reproduction, edited by E. Knobil, J.D. Neill, Raven Press, New York, 1988, pp. 933–974.
Search in Google Scholar Back to article
Bartsch G., Rohr H.P.: Comparative light and electron microscopic study of the human, dog and rat prostate. An approach to an experimental model for human benign prostatic hyperplasia (light and electron microscopic analysis) -a review. Urol Int 1980, 35, 91–104, doi: 10.1159/000280309.
Open DOI Search in Google Scholar Back to article
Borecka P., Ciaputa R., Janus I., Bubak J., Piotrowska A., Ratajczak-Wielgomas K., Podhorska-Okołów M., Dzięgiel P., Nowak M.: Expression of Periostin in Mammary Cancer cells of Female Dogs. In Vivo 2020, 34, 3255–3262, doi: 10.21873/invivo.12162.
Open DOI Search in Google Scholar Back to article
Cheng C.Y., Bardin C.W.: Identification of two testosterone-responsive testicular proteins in Sertoli cell-enriched culture medium whose secretion is suppressed by cells of the intact seminiferous tubule. J Biol Chem 1987, 262, 1268–1277, doi: 10.1016/S0021-9258(18)45273-8.
Open DOI Search in Google Scholar Back to article
Cheng C.Y., Grima J., Stahler M.S., Lockshin R.A., Bardin C.W.: Testins are two structurally related proteins whose secretion is tightly coupled to the presence of germ cells. J Biol Chem 1989, 264, 21386–21393.
Search in Google Scholar Back to article
Coutts A.S.: TES is a novel focal adhesion protein with a role in cell spreading. J Cell Sci 2003, 116, 897–906, doi: 10.1242/jcs.00278.
Open DOI Search in Google Scholar Back to article
Dong R., Pu H., Wang Y., Yu J., Lian K., Mao C.: TESTIN was commonly hypermethylated and involved in the epithelial mesenchymal transition of endometrial cancer. APMIS 2015, 123, 394–400, doi: 10.1111/apm.12361.
Open DOI Search in Google Scholar Back to article
Fawcett D.W.: Male Reproductive System, Volume V, Section 7, Endocrinology: Ultrastructure and Function of the Sertoli cell. In: Handbook of Physiology, edited by D.W. Hamilton, R.O. Greep, American Physiological Society, Washington DC, 1975, pp. 21–55.
Search in Google Scholar Back to article
Giudice C., Banco B., Veronesi M.C., Ferrari A., Di Nardo A., Grieco V.: Immunohistochemical Expression of Markers of Immaturity in Sertoli and Seminal Cells in Canine Testicular Atrophy. J Comp Path 2014, 150, 208–215, doi: 10.1016/j.jcpa.2013.08.001.
Open DOI Search in Google Scholar Back to article
Grieco V., Riccardi E., Veronesi M.C., Giudice C., Finazzi M.: Evidence of testicular dysgenesis syndrome in the dog. Theriogenology 2008, 70, 53–60, doi: 10.1016/j.theriogenology.2008.02.009.
Open DOI Search in Google Scholar Back to article
Grima J., Cheng C.Y.: Testin Is Tightly Associated with Testicular Cell Membrane upon Its Secretion by Sertoli Cells whose Steady-state mRNA Level in the Testis Correlates with the Turnover and Integrity of Intertesticular Cell Junctions. J Biol Chem 1997, 272, 6499–6509, doi: 10.1074/jbc.272.10.6499.
Open DOI Search in Google Scholar Back to article
Grima J., Cheng C.Y.: Testin Induction: The Role of Cyclic 39,59-Adenosine Monophosphate/Protein Kinase A Signaling in the Regulation of Basal and Lonidamine-Induced Testin Expression by Rat Sertoli Cells. Biol Reprod 2000, 63, 1648–1660, doi: 10.1095/biolreprod63.6.1648.
Open DOI Search in Google Scholar Back to article
Grima J., Wong C.C.S., Zhu L.J., Zong S.D., Cheng C.Y.: Testin secreted by Sertoli cells is associated with the cell surface, and its expression correlates with the disruption of Sertoli-germ cell junctions but not the inter-Sertoli tight junction. J Biol Chem 1998, 273, 21040–21053, doi: 10.1074/jbc.273.33.21040.
Open DOI Search in Google Scholar Back to article
Grima J., Zhu L.J., Zong S.D., Catterall J.F., Bardin C.W., Cheng C.Y.: Rat testin is a newly identified component of the junctional complexes in various tissues whose mRNA is predominately expressed in the testis and ovary. Biol Reprod 1995, 52, 340–355, doi: 10.1095/biolreprod52.2.340.
Open DOI Search in Google Scholar Back to article
Gu Z., Ding G., Liang K., Zhang H., Guo G., Zhang L., Cui J.: TESTIN suppresses tumor growth and invasion via manipulating cell cycle progression in endometrial carcinoma. Med Sci Monit 2014, 20, 980–987, doi: 10.12659/MSM.890544.
Open DOI Search in Google Scholar Back to article
Gunduz E., Gunduz M., Beder L., Nagatsuka H., Fukushima K., Sutcu R., Delibas N., Yamanaka N., Shimizu K., Nagai N.: Downregulation of TESTIN and Its Association With Cancer History and a Tendency Toward Poor Survival in Head and Neck Squamous Cell Carcinoma. Arch Otolaryngol Neck Surg 2009, 135, 254, doi: 10.1001/archoto.2008.560.
Open DOI Search in Google Scholar Back to article
Gurzu S., Ciortea D., Ember I., Jung I.: The possible role of mena protein and its splicing-derived variants in embryogenesis, carcinogenesis, and tumor invasion: a systematic review of the literature. Biomed Res Int 2013, 365192, doi: 10.1155/2013/365192.
Open DOI Search in Google Scholar Back to article
Hu K., Huang P., Luo H., Yao Z., Wang Q., Xiong Z., Lin J., Huang H., Xu S., Zhang P., Liu B.: Mammalian-enabled (MENA) protein enhances oncogenic potential and cancer stem cell-like phenotype in hepatocellular carcinoma cells. FEBS Open Bio 2017, 22, 1144–1153, doi: 10.1002/2211-5463.12254.
Open DOI Search in Google Scholar Back to article
Khurana T., Khurana B., Noegel A.A.: LIMproteins: association with the actin cytoskeleton. Protoplasma 2002, 219, 112, doi: 10.1007/s007090200000.
Open DOI Search in Google Scholar Back to article
Li H., Huang K., Gao L., Wang L., Niu Y., Liu H.: TES inhibits colorectal cancer progression through activation of p38. Oncotarget 2016, 7, 45819–45836, doi: 10.18632/oncotarget.9961.
Open DOI Search in Google Scholar Back to article
Ma H., Weng D., Chen Y., Huang W., Pan K., Wang H., Sun J., Wang Q., Zhou Z., Wang H., Xia J.: Extensive analysis of D7S486 in primary gastric cancer supports TESTIN as a candidate tumor suppressor gene. Mol Cancer 2010, 9, 1–10, doi: 10.1186/1476-4598-9-190.
Open DOI Search in Google Scholar Back to article
Pecile A., Groppetti D., Pizzi G., Banco B., Bronzo V., Giudice C., Grieco V.: Immunohistochemical insights into a hidden pathology: Canine cryptorchidism. Theriogenology 2021, 176, 43–53, doi: 10.1016/j.theriogenology.2021.09.011.
Open DOI Search in Google Scholar Back to article
Pelletier R.M., Byers S.W.: The blood-testis barrier and Sertoli cell junctions: structural considerations. Microsc Res Tech 1992, 20, 3–33, doi: 10.1002/jemt.1070200104.
Open DOI Search in Google Scholar Back to article
Popiel A., Kobierzycki C., Dzięgiel P.: The Role of Testin in Human Cancers. Pathol Oncol Res 2019, 25, 1279–1284, doi: 10.1007/s12253-018-0488-3.
Open DOI Search in Google Scholar Back to article
Popiel A., Piotrowska A., Sputa-Grzegrzolka P., Smolarz B., Romanowicz H., Dzięgiel P., Podhorska-Okołów M., Kobierzycki Ch.: Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia. Biomedicines 2021, 13, 1010, doi: 10.3390/biomedicines9081010.
Open DOI Search in Google Scholar Back to article
Qiu H., Zhu J., Yuan C., Yan S., Yang Q., Kong B.: Frequent hypermethylation and loss of heterozygosity of the testis derived transcript gene in ovarian cancer. Cancer Sci 2010, 101, 1255–1260, doi: 10.1111/j.1349-7006.2010.01497.x
Open DOI Search in Google Scholar Back to article
Remmele W., Stegner H.E.: Vorschlag zur einheitlichen Definition eines Immunreaktiven Score (IRS) für den immunhistochemischen Ostrogenrezeptor-Nachweis (ER-ICA) im Mammakarzinomgewebe (Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue – in German). Pathologe 1987, 8, 138–140.
Search in Google Scholar Back to article
Ruetten H., Vezina C.M.: Relevance of dog as an animal model for urologic diseases. Prog Mol Biol Transl Sci 2022, 189, 35– 65, doi: 10.1016/bs.pmbts.2021.12.002.
Open DOI Search in Google Scholar Back to article
Sarti M., Sevignani C., Calin G.A., Aqeilan R., Shimizu M., Pentimalli F., Picchio M.C., Godwin A., Rosenberg A., Drusco A., Negrini M., Croce C.M.: Adenoviral transduction of TESTIN gene into breast and uterine cancer cell lines promotes apoptosis and tumor reduction in vivo. Clin Cancer Res 2005, 11, 806–813, doi: 10.1158/1078-0432.806.11.2.
Open DOI Search in Google Scholar Back to article
Tatarelli C., Linnenbach A., Mimori K., Croce C.M.: Characterization of the human TESTIN gene localized in the FRA7G region at 7q31. Genomics 2000, 12, 1–12, doi: 10.1006/geno.2000.6272.
Open DOI Search in Google Scholar Back to article
Weeks R.J., Ludgate J.L., LeMée G., Morison I.M.: TESTIN induces rapid death and suppresses proliferation in childhood B acute lymphoblastic leukaemia cells. PLoS One 2016, 11, doi: 10.1371/journal.pone.0151341.
Open DOI Search in Google Scholar Back to article
Zachary L., Smith M.D., Ryan P., Werntz M.D., Scott E., Eggener M.D.: Testicular Cancer: Epidemiology, Diagnosis, and Management. Med Clin N 2018, 102, 251–262, doi: 10.1016/j.mcna.2017.10.003.
Open DOI Search in Google Scholar Back to article
Zhong Y., Zhu J., Wang Y., Zhou J., Ren K., Ding X., Zhang J.: LIM domain protein TES changes its conformational states in different cellular compartments. Mol Cell Biochem 2009, 320, 85–92, doi: 10.1007/s11010-008-9901-7.
Open DOI Search in Google Scholar Back to article
Zong S.D., Zhu L.J., Grima J., Aravindan G.R., Bardin C.W., Cheng C.Y.: Cyclic and postnatal developmental changes of testin in the rat seminiferous epithelium – an immunohistochemical study. Biol Reprod 1994, 51, 843–851, doi: 10.1095/biolreprod51.5.843.
Open DOI Search in Google Scholar Back to article