Uterin leiomyomda Wnt, β-katenin, TGF–β, Siklin D1’in Ekspresyon seviyelerinin belirlenmesi

Year 2019, , 138 - 141, 15.09.2019

Halime Hanım Pençe , Özge Kömürcü Karuserci , Esra Güzel Tanoğlu , Mete Gürol Uğur

https://doi.org/10.16948/zktipb.629373

Abstract

Amaç: Uterin leiomyomlar oldukça sık görülen
östrojen ve progesterone bağımlı benign tümörlerdir. Üreme çağındaki kadınlarda
görülebilir ve düzensiz uterin kanama, şiddetli anemi, tekrarlayan gebelik
kaybı gibi ciddi problemlere sebep olurlar. Her leiomyomun, tek bir mutasyona
uğramış myometrial düz kas kök hücresinden kaynaklandığı düşünülmektedir.
Bununla birlikte östrojen/progesteronun leiomyoma büyümesini nasıl düzenlediği
bilinmemektedir. Bu çalışmada Wnt,
β-katenin, TGF–β, siklin D1 genlerinin uterin leiomyom progresyoundaki
etkilerinin gösterilmesi amaçlanmıştır.

Gereç ve
Yöntem: Gaziantep Üniversitesi Tıp
Fakültesi Kadın Hastalıkları ve Doğum Anabilim Dalı’na başvuran ve leiomyoma
tanısı alan 70 hasta ile 66 sağlıklı bireyden alınan dokular  çalışmaya dahil edilmiştir. Hasta ve
sağlıklı gruplar arasında genlerin ekspresyon farklılıkları kantitatif Realtime
PCR ile yapılmıştır.

Bulgular:
Hastaların
ortalama yaşının 44,1±6,8 yıl olduğu bulunmuştur. Sigara içen hasta sayısının toplamda
8% olduğu ve gruplar arasında sigara kullanımı açısından fark olmadığı
saptanmıştır. Uterin leiomyom tanısına sahip hastalarda
Wnt, β-katenin, TGF–β,
siklin D1 genlerinin ekspresyon düzeylerinde sağlıklı
gruba göre belirgin bir artış olduğu istatistiksel olarak tespit edilmiştir.

Sonuç: Bu çalışmada Wnt, β-katenin, TGF–β, siklin
D1’in östrojen/progesteron’un leiomyoma oluşumu ve büyümesinde kritik bir
parakrin rolü olduğunu ortaya konulmuştur.

Keywords

Leiomyom, uterus, TGF–β; Wnt; B-katenin; Siklin D1

Supporting Institution

Sağlık Bilimleri Üniversitesi, Bilimsel Araştırma Projesi

Project Number

2018/055

Thanks

Bu çalışma Sağlık Bilimleri Üniversitesi, Bilimsel Araştırma Projesi tarafından desteklenmiştir. (Proje No: 2018/055)

Determination of Wnt, β-catenin, TGF – β and Cyclin D1 expression levels in uterine leiomyoma

Abstract

Objective:
Uterine leiomyomas are common estrogen and progesterone-dependent
benign tumors. They occur in women of reproductive age and cause serious
problems such as irregular uterine bleeding, severe anemia, recurrent pregnancy
loss. Each leiomyoma is thought to originate from a single mutated myometrial smooth
muscle stem cell. However, it is not known how estrogen / progesterone
regulates the growth of leiomyoma. The aim of this study was to show the
effects of Wnt, β-catenin, TGF – β, cyclin D1 genes on uterine leiomyoma
progression.

Materials
and Methods: Tissues from 70 patients and 66
healthy individuals who were admitted to Gaziantep University Faculty of
Medicine, Department of Obstetrics and Gynecology and diagnosed as leiomyoma
were included in the study. Differences in the expression of genes between
patient 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 the
groups in terms of smoking. The expression levels of Wnt, β-catenin, TGF – β,
and cyclin D1 genes were significantly increased in patients with uterine
leiomyoma 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 and
growth of leiomyoma of estrogen / progesterone    

Keywords

Leiomyoma, uterus, TGF-β, Wnt, B-catenin, Cyclin D1

Project Number

2018/055

References

• 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.
• 2. De La Cruz, M.S. and E.M. Buchanan, Uterine Fibroids: Diagnosis and Treatment. Am Fam Physician, 2017. 95(2): p. 100-107.
• 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.
• 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.
• 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.
• 6. Jordan, C.T., M.L. Guzman, and M. Noble, Cancer stem cells. N Engl J Med, 2006. 355(12): p. 1253-61.
• 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.
• 8. Ono, M., et al., Role of stem cells in human uterine leiomyoma growth. PLoS One, 2012. 7(5): p. e36935.
• 9. Gupta, S., J. Jose, and I. Manyonda, Clinical presentation of fibroids. Best Pract Res Clin Obstet Gynaecol, 2008. 22(4): p. 615-26.
• 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.
• 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.
• 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.
• 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.
• 14. Kim, S., et al., Mediator is a transducer of Wnt/beta-catenin signaling. J Biol Chem, 2006. 281(20): p. 14066-75.
• 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.
• 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.
• 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.
• 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.
• 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.
• 21. Yang, J., et al., Genetic aberrations in soft tissue leiomyosarcoma. Cancer Lett, 2009. 275(1): p. 1-8.