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RNA inference-mediated caveolin-1 down-regulation decrease estrogen receptor alpha (ERα) signaling in human mammary epithelial cells

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Abstract

Several evidences support that caveolin-1 is associated with mammary cell transformation and oncogenesis. We have previously reported that a cell line, named MCF10A-ST1 (ST1), which only expressed 30% Cav-1 compared with parental cells MCF10A (human mammary epithelial cell line) was isolated by gene trapping. The decreased expression of Cav-1 is sufficient for phenotypic transformation of MCF10A cells, which involved in the loss of anchorage-dependent growth and migration in nude mice with the existence of E2. The previous study in our lab on microarray assay showed that the expression of cyclin D1 (cell cycle protein) was up-regulated in ST1 cell line. Here, we not only confirmed the results by Western Blot but also demonstrated that Cav-1 down-regulation accelerate the progression of mammary cells from G1 phase into S phase by Flow Cytometry (FCM). This proposed that the Cav-1 down-regulation could change the progress of cell cycle in the mammary cells. Otherwise, microarray assay also showed that the transcription factor (c-Jun) was up-regulated. But, the original carcinoma gene (c-Fos) and transcription factor (AP-1) have not obviously changed compared with MCF10A. ST1 cells obtained the morigenicity in nude mice with the existence of E2, and the immunoprecipitation showed the interactions of Cav-1 with ERα in both MCF10A and ST1. ERα expression was increased as further down-regulation of Cav-1. So, we hypothesize that Cav-1 down-regulation could induce the activation of ERα-associated signaling pathway, in order to adjust the development and proliferation. By siRNA technology, the down regulation of Cav-1 could activate MAP kinase and Akt signaling pathway, including the phosphorylation of ERK1/2 and Akt. However, the mechanism of Cav-1 down-regulation in the early transformation and signaling transduction of mammary epithelial cells is unclear. Here, we report that down-regulation of caveolin-1 protein expression leads to deregulate estrogen receptor alpha (ERα) signaling and consequently early transformation in mammary epithelia.

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References

  1. Schlegel A, Lisanti MP (2001) Caveolae and their coat proteins, the caveolins: from electron microscopic novelty to biological launching pad. J Cell Physiol 186:329–337

    Article  CAS  PubMed  Google Scholar 

  2. Thomas CM, Smart EJ (2008) Caveolae structure and function. J Cell Mol Med 12(3):796–809

    Article  CAS  PubMed  Google Scholar 

  3. Engelman JA, Zhang X, Galbiati F et al (1998) Chromosomal localization, genomic organization, and developmental expression of the murine caveolin gene family (Cav-1, -2 and -3). Cav-1 and Cav-2 gene map to a known suppressor locus (6-A2/7q31). FEBS Lett 429:330–336

    Article  CAS  PubMed  Google Scholar 

  4. Razani B, Woodman SE, Lisanti MP (2002) Caveolae from cell biology to animal physiology. Pharmacol Rev 54:431–467

    Article  CAS  PubMed  Google Scholar 

  5. Chatenay-Rivauday C, Cakar ZP, Jeno P et al (2004) Caveolae: biochemical analysis. Mol Biol Rep 31(2):67–84

    Article  CAS  PubMed  Google Scholar 

  6. Li S, Couet J, Lisanti MP (1996) Src tyrosine kinases, G alpha subunits and H-Ras share a common membrane regulates the auto-activation of Src tyrosine kinases. J Biol Chem 271:29182–29190

    Article  CAS  PubMed  Google Scholar 

  7. Engelman JA, Lee RJ, Karnezis A et al (1998) Reciprocal regulation of Neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implication for mammary tumorigenesis. J Biol Chem 273:20448–20455

    Article  CAS  PubMed  Google Scholar 

  8. Williams TM, Lisanti MP (2005) Caveolin-1 in oncogenic transformation, cancer, and metastasis. Am J Physiol Cell Physiol 288:494–506

    Article  Google Scholar 

  9. Kimbro KS, Duschene K, Willard M et al (2008) A novel gene STYK1/NOK is upregulated in estrogen receptor-alpha negative estrogen receptor-beta positive breast cancer cells following estrogen treatment. Mol Biol Rep 35(1):23–27

    Article  CAS  PubMed  Google Scholar 

  10. Tianhong L, Federica S, Magalis AV et al (2006) Caveolin-1 mutations in human breast cancer: functional association with estrogen receptor α-positive status. Am J Pathol 168(6):1998–2013

    Article  Google Scholar 

  11. Stephen RH, Ellis RL et al (2007) Extranuclear steroid receptor : nature and actions. Endocr Rev 28(7):726–741

    Article  Google Scholar 

  12. Singh RR, Kumar R (2005) Steroid hormone receptor signaling in tumorigenesis. J Cell Biochem 96:490–505

    Article  CAS  PubMed  Google Scholar 

  13. Lee RJ et al (2000) Cyclin D1 is required for transformation by activated Neu and is induced through an E2F-dependent signaling pathway. Mol Cell Biol 20:672–683

    Article  CAS  PubMed  Google Scholar 

  14. Pia B, Mirva S, Tuire P, Pirkko H et al (2009) Analysis of cyclins A, B1, D1 and E in breast cancer in relation to tumour grade and other prognostic factors. BMC Res Notes 2(1):140

    Article  Google Scholar 

  15. Karin M (1995) The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270:16483–16486

    CAS  PubMed  Google Scholar 

  16. Passegue E, Jchum W, Schmpp-Kistner M et al (2001) Chronic myeloid leukemia with increased granulocyte progenitors in mice lacking junB expression in the myeloid lineage. Cell 104:21–32

    Article  CAS  PubMed  Google Scholar 

  17. Dong GH, Peter IM (2009) Estrogen receptor α, Fos-related antigen-2, and c-Jun coordinately regulate human UDP glucuronosyltransferase 2B15 and 2B17 expression in response to 17β-estradiol in MCF-7 cells. Mol Pharmacol 76:425–439

    Article  Google Scholar 

  18. Arteaga CL, Holt JT (1996) Tissue-targeted antisense c-fos retroviral vector inhibits established breast cancer xenografts in nude mice. Cancer Res 56:1098–1103

    CAS  PubMed  Google Scholar 

  19. English J, Pearson G, Wilsbacher J et al (1999) New insights into the control of MAP kinase pathways. Exp Cell Res 253:255–270

    Article  CAS  PubMed  Google Scholar 

  20. Migliaccio A, Di Domenico M, Castoria G et al (1997) Rapid membrane effects of steroids in neuroblastoma cells: effects of estrogen and mitogen activated protein kinase signaling cascade and C-Fos immediate early gene transcription. Endocrinology 138:4030–4033

    Article  Google Scholar 

  21. Zivadinovic D, Watson CS (2005) Membrane estrogen receptor-α levels predict estrogen-induced ERK1/2 activation in MCF-7 cells. Breast Cancer Res 7:130–144

    Article  Google Scholar 

  22. Ikeyama S, Kokkonen G, Shack S et al (2002) Loss in oxidative stress tolerance with aging linked to reduced extracellular signal-regulated kinase and Akt kinase activities. FASEB J 16:114–116

    CAS  PubMed  Google Scholar 

  23. Yao R, Cooper GM (1995) Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267:2003–2006

    Article  CAS  PubMed  Google Scholar 

  24. Fujio Y, Nguyen T, Wencker D et al (2000) Akt promotes survival of cardiomyocytes in vitro and protects against ischemia reperfusion injury in mouse heart. Circulation 101:660–667

    CAS  PubMed  Google Scholar 

  25. Andrea V, Lorena M, Ricardo B (2008) 17β-Estradiol abrogates apoptosis in murine skeletal muscle cells through estrogen receptors: role of the phosphatidylinositol 3-kinase/Akt pathway. J Endocrinol 196:385–397

    Article  Google Scholar 

  26. Zou W, Mcdaneld L, Smith LM et al (2003) Caveolin-1 haplo insufficiency leads to partial transformation of human breast epithelial cells. Anticancer Res 23(6C):4581–4586

    CAS  PubMed  Google Scholar 

  27. Russell KS, Haynes MP, Sinha D et al (2000) Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proc Natl Acad Sci USA 97:5930–5935

    Article  CAS  PubMed  Google Scholar 

  28. Razandi M, Oh P, Pedram A et al (2002) ERs associate with and regulate the production of caveolin: implications for signaling and cellular actions. Mol Endocrinol 16(1):100–115

    Article  CAS  PubMed  Google Scholar 

  29. Zivadinovic D, Watson CS (2005) Membrane estrogen receptor-α levels predict estrogen-induced ERK1/2 activation in MCF-7 cells. Breast Cancer Res 7:130–144

    Article  Google Scholar 

  30. Milde-Langosch K, Bamberger AM, Methner C et al (2000) Expression of cell cycle-regulator proteins rb, p16/MTS1, p27/KIP1, p21/WAF1, cyclin D1 and cyclin E in breast cancer: correlation with expression of activating protein-1 family members. Int J Cancer 87:468–472

    Article  CAS  PubMed  Google Scholar 

  31. Marino M, Distefano E, Pallottini V et al (2001) β-Estradiol stimulation of DNA synthesis requires different PKC isoforms in HepG2 and MCF-7 cells. J Cell Physiol 188:170–177

    Article  CAS  PubMed  Google Scholar 

  32. Razandi M, Pedram A, Levin ER (2000) Plasma membrane estrogen receptors signal to antiapoptosis in breast cancer. Mol Endocrinol 14:1434–1447

    Article  CAS  PubMed  Google Scholar 

  33. Acconcia F, Ascenzi P, Bocedi A et al (2005) Palmitoylation-dependent estrogen receptor α membrane localization: regulation by 17β-estradiol. Mol Biol Cell 16:231–237

    Article  CAS  PubMed  Google Scholar 

  34. Milde-Langosch K, Kappes H, Riethdorf S et al (2003) Fos B is highly expressed in normal mammary epithelia, but down-regulated in poorly differentiated breast carcinomas. Breast Cancer Res Treat 77:265–275

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 30570225).

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Authors and Affiliations

  1. College of Life Science, Liaoning Normal University, 116029, Dalian, China

    Xi Wang, Shuang Feng, Hong Zhang, Yang Wang, Yuying Cui & Wei Zou

  2. Liaoning Key Laboratories of Biotechnology and Molecular Drug Research and Development, 116029, Dalian, China

    Wei Zou

  3. Cancer Center, Creighton University, 2500 California Plaza, Omada, NE, 68178, USA

    Zhaoyi Wang

  4. First Clinical Hospital of Dalian Medical University, 116011, Dalian, China

    Jing Liu

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  1. Xi Wang
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Correspondence to Wei Zou.

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Wang, X., Feng, S., Zhang, H. et al. RNA inference-mediated caveolin-1 down-regulation decrease estrogen receptor alpha (ERα) signaling in human mammary epithelial cells. Mol Biol Rep 38, 761–768 (2011). https://doi.org/10.1007/s11033-010-0164-5

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  • DOI: https://doi.org/10.1007/s11033-010-0164-5

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