TY  - JOUR
T1  - Uterin leiomyomda Wnt, β-katenin, TGF–β, Siklin D1’in Ekspresyon seviyelerinin belirlenmesi
TT  - Determination of Wnt, β-catenin, TGF – β and Cyclin D1 expression levels in uterine leiomyoma
AU  - Güzel Tanoğlu, Esra
AU  - Pençe, Halime Hanım
AU  - Kömürcü Karuserci, Özge
AU  - Uğur, Mete Gürol
PY  - 2019
DA  - September
DO  - 10.16948/zktipb.629373
JF  - Zeynep Kamil Tıp Bülteni
PB  - Zeynep Kamil Kadın ve Çocuk Hastalıkları EAH
WT  - DergiPark
SN  - 1300-7971
SP  - 138
EP  - 141
VL  - 50
IS  - 3
LA  - tr
AB  - Amaç:Uterin leiomyomlar oldukça sık görülenöstrojen ve progesterone bağımlı benign tümörlerdir. Üreme çağındaki kadınlardagörülebilir ve düzensiz uterin kanama, şiddetli anemi, tekrarlayan gebelikkaybı gibi ciddi problemlere sebep olurlar. Her leiomyomun, tek bir mutasyonauğramış myometrial düz kas kök hücresinden kaynaklandığı düşünülmektedir.Bununla birlikte östrojen/progesteronun leiomyoma büyümesini nasıl düzenlediğibilinmemektedir. Bu çalışmada Wnt,β-katenin, TGF–β, siklin D1 genlerinin uterin leiomyom progresyoundakietkilerinin gösterilmesi amaçlanmıştır. Gereç veYöntem: Gaziantep Üniversitesi TıpFakültesi Kadın Hastalıkları ve Doğum Anabilim Dalı’na başvuran ve leiomyomatanısı alan 70 hasta ile 66 sağlıklı bireyden alınan dokular çalışmaya dahil edilmiştir. Hasta vesağlıklı gruplar arasında genlerin ekspresyon farklılıkları kantitatif RealtimePCR ile yapılmıştır.Bulgular:Hastalarınortalama yaşının 44,1±6,8 yıl olduğu bulunmuştur. Sigara içen hasta sayısının toplamda8% olduğu ve gruplar arasında sigara kullanımı açısından fark olmadığısaptanmıştır. Uterin leiomyom tanısına sahip hastalardaWnt, β-katenin, TGF–β,siklin D1genlerinin ekspresyon düzeylerinde sağlıklıgruba göre belirgin bir artış olduğu istatistiksel olarak tespit edilmiştir.Sonuç: Bu çalışmada Wnt, β-katenin, TGF–β, siklinD1’inöstrojen/progesteron’un leiomyoma oluşumu ve büyümesinde kritik birparakrin rolü olduğunu ortaya konulmuştur.
KW  - Leiomyom
KW  - uterus
KW  - TGF–β; Wnt; B-katenin; Siklin D1
N2  - Objective:Uterine leiomyomas are common estrogen and progesterone-dependentbenign tumors. They occur in women of reproductive age and cause seriousproblems such as irregular uterine bleeding, severe anemia, recurrent pregnancyloss. Each leiomyoma is thought to originate from a single mutated myometrial smoothmuscle stem cell. However, it is not known how estrogen / progesteroneregulates the growth of leiomyoma. The aim of this study was to show theeffects of Wnt, β-catenin, TGF – β, cyclin D1 genes on uterine leiomyomaprogression.Materialsand Methods: Tissues from 70 patients and 66healthy individuals who were admitted to Gaziantep University Faculty ofMedicine, Department of Obstetrics and Gynecology and diagnosed as leiomyomawere included in the study. Differences in the expression of genes betweenpatient and healthy groups were performed by quantitative Realtime PCR.Results: The mean age of the patients was 44.1 ± 6.8 years.The total number of smokers was 8% and there was no difference between thegroups in terms of smoking. The expression levels of Wnt, β-catenin, TGF – β,and cyclin D1 genes were significantly increased in patients with uterineleiomyoma compared to healthy group.Conclusion: In this study, it was demonstrated that Wnt,β-catenin, TGF sik β and cyclin D1 play a critical role in the formation andgrowth of leiomyoma of estrogen / progesterone
CR  - 1.	Styer, A.K. and B.R. Rueda, The Epidemiology and Genetics of Uterine Leiomyoma. Best Pract Res Clin Obstet Gynaecol, 2016. 34: p. 3-12.
CR  - 2.	De La Cruz, M.S. and E.M. Buchanan, Uterine Fibroids: Diagnosis and Treatment. Am Fam Physician, 2017. 95(2): p. 100-107.
CR  - 3.	Szotek, P.P., et al., Adult mouse myometrial label-retaining cells divide in response to gonadotropin stimulation. Stem Cells, 2007. 25(5): p. 1317-25.
CR  - 4.	Schwab, K.E., P. Hutchinson, and C.E. Gargett, Identification of surface markers for prospective isolation of human endometrial stromal colony-forming cells. Hum Reprod, 2008. 23(4): p. 934-43.
CR  - 5.	Schofield, R., The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells, 1978. 4(1-2): p. 7-25.
CR  - 6.	Jordan, C.T., M.L. Guzman, and M. Noble, Cancer stem cells. N Engl J Med, 2006. 355(12): p. 1253-61.
CR  - 7.	Mas, A., et al., Identification and characterization of the human leiomyoma side population as putative tumor-initiating cells. Fertil Steril, 2012. 98(3): p. 741-751.e6.
CR  - 8.	Ono, M., et al., Role of stem cells in human uterine leiomyoma growth. PLoS One, 2012. 7(5): p. e36935.
CR  - 9.	Gupta, S., J. Jose, and I. Manyonda, Clinical presentation of fibroids. Best Pract Res Clin Obstet Gynaecol, 2008. 22(4): p. 615-26.
CR  - 10.	Mäkinen, N., et al., MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science, 2011. 334(6053): p. 252-5.
CR  - 11.	Al-Hendy, A., et al., Silencing Med12 Gene Reduces Proliferation of Human Leiomyoma Cells Mediated via Wnt/β-Catenin Signaling Pathway. Endocrinology, 2017. 158(3): p. 592-603.
CR  - 12.	Markowski, D.N., et al., MED12 mutations in uterine fibroids--their relationship to cytogenetic subgroups. Int J Cancer, 2012. 131(7): p. 1528-36.
CR  - 13.	Markowski, D.N., et al., Uterine fibroids: do we deal with more than one disease? Int J Gynecol Pathol, 2014. 33(6): p. 568-72.
CR  - 14.	Kim, S., et al., Mediator is a transducer of Wnt/beta-catenin signaling. J Biol Chem, 2006. 281(20): p. 14066-75.
CR  - 15.	Ono, M., et al., Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Proc Natl Acad Sci U S A, 2013. 110(42): p. 17053-8.
CR  - 16.	Lee, B.S. and R.A. Nowak, Human leiomyoma smooth muscle cells show increased expression of transforming growth factor-beta 3 (TGF beta 3) and altered responses to the antiproliferative effects of TGF beta. J Clin Endocrinol Metab, 2001. 86(2): p. 913-20.
CR  - 17.	Arici, A. and I. Sozen, Expression, menstrual cycle-dependent activation, and bimodal mitogenic effect of transforming growth factor-beta1 in human myometrium and leiomyoma. Am J Obstet Gynecol, 2003. 188(1): p. 76-83.
CR  - 18.	Norian, J.M., et al., Transforming growth factor beta3 regulates the versican variants in the extracellular matrix-rich uterine leiomyomas. Reprod Sci, 2009. 16(12): p. 1153-64.
CR  - 19.	Mäkinen, N., et al., MED12 exon 2 mutations are common in uterine leiomyomas from South African patients. Oncotarget, 2011. 2(12): p. 966-9.20.	Sherr, C.J., Cancer cell cycles. Science, 1996. 274(5293): p. 1672-7.
CR  - 21.	Yang, J., et al., Genetic aberrations in soft tissue leiomyosarcoma. Cancer Lett, 2009. 275(1): p. 1-8.
UR  - https://doi.org/10.16948/zktipb.629373
L1  - https://dergipark.org.tr/en/download/article-file/834138
ER  -