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Gene expression and tyrosine kinase activity of insulin receptor in uterine leiomyoma and matched myometrium

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Abstract

Objective

Our objective was to determine the insulin receptor (IR) mRNA levels and IR tyrosine kinase activity in normal myometrium and leiomyoma.

Design

Experimental study.

Setting

Academic research center.

Patients

Five women with leiomyoma submitted to hysterectomy.

Intervention

Plasma membrane fraction of human myometrium and leiomyoma were prepared and samples were incubated with and without insulin. mRNA was isolated and RT-PCR with specific primers was performed.

Main outcome measure

Western blots of plasma membranes incubated with and without insulin were performed. Chemoluminescent methods followed by densitometry were used to assess IR autophosphorylation. RT-PCR with specific primers for IR gene sequences was used to determine IR mRNA levels.

Results

IR mRNA levels in myometrium (0.634±0.038) and in leiomyoma (0.649±0.047; p=0.813) were not different. The degree of insulin-stimulated IR autophosphorylation (relative optical density of the 95 kDa band) was also not different between myometrium (1.496±0.310) and leiomyoma (1.593±0.129; p=0.650).

Conclusions

There was no difference in IR receptor expression and IR autophosphorylation between normal myometrium and leiomyoma. Other steps of insulin signaling chain may participate in the altered proliferation of leiomyomas.

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References

  1. Capp E, Brandelli A, Monego H, Ribeiro MF, de Freitas MS, Pureur R, Tortorela H (1996) Binding and tyrosine kinase activity of insulin receptor in human normal and neoplastic endometrium. Med Sci Res 24:621–623

    CAS  Google Scholar 

  2. Chandrasekhar Y, Heiner J, Osuamkpe C, Nagamani M (1992) Insulin-like growth factor I and II binding in human myometrium and leiomyomas. Am J Obstet Gynecol 166:64–69

    CAS  Google Scholar 

  3. Cheatham B, Kahn CR (1995) Insulin action and the insulin signaling network. Endocr Rev 16:117–142

    PubMed  Google Scholar 

  4. Corleta HE, Capp E, Corleta OC (1996) Insulin receptor tyrosine kinase activity in colon carcinoma. Braz J Med Biol Res 29:1593–1597

    CAS  Google Scholar 

  5. De Leo V, la Marca A, Morgante G, Severi FM, Petraglia F (2001) Administration of somatostatin analogue reduces uterine and myoma volume in women with uterine leiomyomata. Fertil Steril 75:632–633

    Article  PubMed  Google Scholar 

  6. Dupont J, LeRoith D (2001) Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res 55 [Suppl 2]:22–26

    Google Scholar 

  7. Englund K, Lindblom B, Carlstrom K, Gustavsson I, Sjoblom P, Blanck A (2000) Gene expression and tissue concentrations of IGF-I in human myometrium and fibroids under different hormonal conditions. Mol Hum Reprod 6:915–920

    CAS  Google Scholar 

  8. Fayed YM, Tsibris JC, Langenberg PW, Robertson AL (1989) Human uterine leiomyoma cells: binding and growth responses to epidermal growth factor, platelet-derived growth factor, and insulin. Lab Invest 60:30–37

    CAS  Google Scholar 

  9. Giudice LC, Irwin JC, Dsupin BA, Pannier EM, Jin IH, Vu TH (1993) Insulin-like growth factor (IGF), IGF binding protein (IGFBP), and IGF receptor gene expression and IGFBP synthesis in human uterine leiomyomata. Hum Reprod 8:1796–1806

    CAS  Google Scholar 

  10. Harrison-Woolrych ML, Charnock-Jones DS, Smith SK (1994) Quantification of messenger ribonucleic acid for epidermal growth factor in human myometrium and leiomyomata using reverse transcriptase polymerase chain reaction. J Clin Endocrinol Metab 78:1179–1184

    CAS  Google Scholar 

  11. Kellerer M, von Eye Corleta H, Muhlhofer A, Capp E, Mosthaf L, Bock S et al (1995) Insulin- and insulin-like growth-factor-I receptor tyrosine-kinase activities in human renal carcinoma. Int J Cancer 62:501–507

    CAS  Google Scholar 

  12. Kurachi O, Matsuo H, Samoto T, Maruo T (2001) Tumor necrosis factor-alpha expression in human uterine leiomyoma and its down-regulation by progesterone. J Clin Endocrinol Metab 86:2275–2280

    CAS  Google Scholar 

  13. Liu HC, He ZY, Tang YX (1997) Simultaneous detection of multiple gene expression in mouse and human individual preimplantation embryos. Fertil Steril 67:733–741

    CAS  Google Scholar 

  14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with folic phenol reagent. J Biol Chem 193:265–275

    CAS  Google Scholar 

  15. Maruo T, Matsuo H, Samoto T, Shimomura Y, Kurachi O, Gao Z et al (2001) Effects of progesterone on uterine leiomyoma growth and apoptosis. Steroids 65:585–592

    Article  Google Scholar 

  16. Moran C, Huerta R, Conway-Myers BA, Hines GA, Azziz R (2001) Altered autophosphorylation of the insulin receptor in the ovary of a woman with polycystic ovary syndrome. Fertil Steril 75:625–628

    CAS  Google Scholar 

  17. Nagamani M, Stuart CA (1992) Specific binding sites for insulin in the human myometrium and leiomyomas of the uterus. Fertil Steril 58:120–123

    CAS  Google Scholar 

  18. Pandini G, Vigneri R, Costantino A, Frasca F, Ippolito A, Fujita-Yamaguchi Y et al (1999) Insulin and insulin-like growth factor-I (IGF-I) receptor overexpression in breast cancers leads to insulin/IGF-I hybrid receptor overexpression: evidence for a second mechanism of IGF-I signaling. Clin Cancer Res 5:1935–1944

    CAS  Google Scholar 

  19. Sale EM, Atkinson PP, Arnott CH, Chad JE, Sale GJ (1999) Role of ERK1/ERK2 and p70S6 K pathway in insulin signalling of protein synthesis. FEBS Lett 446:122–126

    CAS  Google Scholar 

  20. Seedorf K (1995) Intracellular signaling by growth factors. Metabolism 44:24–32

    CAS  Google Scholar 

  21. Silva IS, Morsch DM, Urnauer L, Spritzer PM (2001) Androgen-induced cell growth and c-myc expression in human non-transformed epithelial prostatic cells in primary culture. Endocr Res 27:153–169

    CAS  Google Scholar 

  22. Stewart EA (2001) Uterine fibroids. Lancet 357:293–298

    Article  CAS  PubMed  Google Scholar 

  23. Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK et al (1995) Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 332:1393–1398

    CAS  Google Scholar 

  24. Vollenhoven BJ, Herington AC, Healy DL (1995) Epidermal growth factor and transforming growth factor-beta in uterine fibroids and myometrium. Gynecol Obstet Invest 40:120–124

    CAS  Google Scholar 

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Acknowledgements

Financial support: FAPERGS, FIPE/HCPA, PROPESQ/UFRGS.

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Correspondence to Edison Capp.

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Toscani, G.K., Chaves, E.M., Cervi, F.L. et al. Gene expression and tyrosine kinase activity of insulin receptor in uterine leiomyoma and matched myometrium. Arch Gynecol Obstet 270, 170–173 (2004). https://doi.org/10.1007/s00404-003-0534-5

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  • DOI: https://doi.org/10.1007/s00404-003-0534-5

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