p27kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis

详细信息    查看全文

• 作者：G. A. Gon?alves ; C. M. Camargo-Kosugi ; T. C. S. Bonetti ; A. L. Invitti…
• 关键词：p27kip1 ; VEGF ; Endometriosis ; Endometrium
• 刊名：Apoptosis
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：20
• 期：3
• 页码：327-335
• 全文大小：642 KB
• 参考文献：1. Giudice LC, Kao LC (2004) Endometriosis. Lancet 364(9447):1789-799 ternal" href="http://dx.doi.org/10.1016/S0140-6736(04)17403-5" target="_blank" title="It opens in new window">CrossRef
  2. Gazvani R, Templeton A (2002) New considerations for the pathogenesis of endometriosis. Int J Gynaecol Obstet 76(2):117-26 ternal" href="http://dx.doi.org/10.1016/S0020-7292(01)00577-X" target="_blank" title="It opens in new window">CrossRef
  3. Missmer SA, Cramer DW (2003) The epidemiology of endometriosis. Obstet Gynecol Clin North Am 30(1):1-9, vii ternal" href="http://dx.doi.org/10.1016/S0889-8545(02)00050-5" target="_blank" title="It opens in new window">CrossRef
  4. Carter JE (1994) Combined hysteroscopic and laparoscopic findings in patients with chronic pelvic pain. J Am Assoc Gynecol Laparosc 2(1):43-7 ternal" href="http://dx.doi.org/10.1016/S1074-3804(05)80830-8" target="_blank" title="It opens in new window">CrossRef
  5. Carter JE (1994) Laparoscopic treatment for chronic pelvic pain: results from three-year follow-up. J Am Assoc Gynecol Laparosc 1(4, Part 2):S6–S7 ternal" href="http://dx.doi.org/10.1016/S1074-3804(05)80812-6" target="_blank" title="It opens in new window">CrossRef
  6. Sampson JA (1927) Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:422-69
  7. Kianpour M, Nematbakhsh M, Ahmadi SM, Jafarzadeh M, Hajjarian M, Pezeshki Z, Safari T, Eshraghi-Jazi F (2013) Serum and peritoneal fluid levels of vascular endothelial growth factor in women with endometriosis. Int J Fertil Steril. 7(2):96-9
  8. McLaren J (2000) Vascular endothelial growth factor and endometriotic angiogenesis. Hum Reprod Update 6(1):45-5 ternal" href="http://dx.doi.org/10.1093/humupd/6.1.45" target="_blank" title="It opens in new window">CrossRef
  9. May KE, Villar J, Kirtley S et al (2011) Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Hum Reprod Update 17(5):637-53 ternal" href="http://dx.doi.org/10.1093/humupd/dmr013" target="_blank" title="It opens in new window">CrossRef
  10. Braun-Dullaeus RC, Mann MJ, Dzau VJ (1998) Cell cycle progression: new therapeutic target for vascular proliferative disease. Circulation 98(1):82-9 ternal" href="http://dx.doi.org/10.1161/01.CIR.98.1.82" target="_blank" title="It opens in new window">CrossRef
  11. Machado DE, Berardo PT, Palmero CY et al (2010) Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases. J Exp Clin Cancer Res 29:4 ternal" href="http://dx.doi.org/10.1186/1756-9966-29-4" target="_blank" title="It opens in new window">CrossRef
  12. Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501-512 ternal" href="http://dx.doi.org/10.1101/gad.13.12.1501" target="_blank" title="It opens in new window">CrossRef
  13. Tsihlias J, Kapusta L, Slingerland J (1999) The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer. Annu Rev Med 50:401-23 ternal" href="http://dx.doi.org/10.1146/annurev.med.50.1.401" target="_blank" title="It opens in new window">CrossRef
  14. Besson A, Gurian-West M, Schmidt A et al (2004) p27Kip1 modulates cell migration through the regulation of RhoA activation. Genes Dev 18(8):862-76 ternal" href="http://dx.doi.org/10.1101/gad.1185504" target="_blank" title="It opens in new window">CrossRef
  15. Velarde MC, Aghajanova L, Nezhat CR et al (2009) Increased mitogen-activated protein kinase kinase/extracellularly regulated kinase activity in human endometrial stromal fibroblasts of women with endometriosis reduces 3-5-cyclic adenosine 5-monophosphate inhibition of cyclin D1. Endocrinology 150(10):4701-712 ternal" href="http://dx.doi.org/10.1210/en.2009-0389" target="_blank" title="It opens in new window">CrossRef
  16. Charnock-Jones DS, Sharkey AM, Rajput-Williams J et al (1993) Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. Biol Reprod 48(5):1120-128 ternal" href="http://dx.doi.org/10.1095/biolreprod48.5.1120" target="_blank" title="It opens in new window">CrossRef
  17. Russo AA, Jeffrey PD, Patten AK et al (1996) Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature 382(6589):325-31 ternal" href="http://dx.doi.org/10.1038/382325a0" target="_blank" title="It opens in new window">CrossRef
  18. Chu IM, Hengst L
• 作者单位：G. A. Gon?alves (1) (2)
  C. M. Camargo-Kosugi (1)
  T. C. S. Bonetti (1)
  A. L. Invitti (1)
  M. J. B. C. Gir?o (1) (2)
  I. D. C. G. Silva (1)
  E. Schor (1)
  
  1. Molecular and Proteomics Gynecology Cellular and Viral Vectors Laboratory, Department of Gynecology, Federal University of S?o Paulo, Escola Paulista de Medicina (UNIFESP-EPM), Rua Mirassol 227, Vila Clementino, S?o Paulo, SP, 04039-002, Brazil
  2. Charitable Association of Blood Collection-COLSAN, Avenida Jandira, 1260 Indianópolis, S?o Paulo, SP, 04080-006, Brazil
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Cell Biology
  Biochemistry
  Virology
  
• 出版者：Springer Netherlands
• ISSN：1573-675X

文摘

We hypothesized that p27kip1 overexpression can regulate endometriosis cell proliferation, apoptosis and vascular endothelial growth factor (VEGF) expression in the endometrium. The overexpression of p27kip1 was obtained by transduction of p27kip1 in primary cultures of endometrium obtained from women with endometriosis tissue with gene therapy technology. First generation bicistronic adenovirus: AdCMVhp27IRESEGFP (Adp27) and AdCMVNull (AdNull) were engineered in order to induce p27kip1 expression in endometrial cells primary culture. The effect of p27kip1 overexpression was elucidated through the cell proliferation evaluation and the expression of the cell cycle-related proteins p16, p21, p27, and p53. Cell cycle and apoptosis in endometrial cells from women with and without endometriosis were also evaluated. The VEGF levels were evaluated 1 and 7?days after transduction. The experiments were performed using Immunofluorescence stainings and flow cytometry technique. The cell proliferation statistically diminished markedly following p27kip1 overexpression in the endometriosis group. This process was accompanied, however, by a statistically significant modulation of the cell cycle-related proteins p16, p21, p27 and p53 markedly increase following p27kip1 overexpression in the endometriosis group (p?VEGF expression was observed 7?days after p27kip1 overexpression, attaining levels strikingly similar to those observed in the control endometrial cells. The findings of this study showed a link between the cell cycle control protein (p27kip1) and angiogenesis (VEGF). Our results, also reinforces the background of endometrial dysfunction as part of the origin of endometriosis. We believe that better knowledge of endometrium milieu and the establishment of the link between different, previously describe, altered pathways in this tissue can facilitate future genetic cell therapy.