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Cyr61 promotes breast tumorigenesis and cancer progression

Abstract

Cyr61, a member of the CCN family of genes, is an angiogenic factor. We have shown that it is overexpressed in invasive and metastatic human breast cancer cells and tissues. Here, we investigated whether Cyr61 is necessary and/or sufficient to bypass the ‘normal’ estrogen (E2) requirements for breast cancer cell growth. Our results demonstrate that Cyr61 is sufficient to induce MCF-7 cells to grow in the absence of E2. Cyr61-transfected MCF-7 cells (MCF-7/Cyr61) became E2-independent but still E2-responsive. On the other hand, MCF-7 cells transfected with the vector DNA (MCF-7/V) remain E2-dependent. MCF-7/Cyr61 cells acquire an antiestrogen-resistant phenotype, one of the most common clinical occurrences during breast cancer progression. MCF-7/Cyr61 cells are anchorage-independent and capable of forming Matrigel outgrowth patterns in the absence of E2. ERα expression in MCF-7/Cyr61 cells is decreased although still functional. Moreover, MCF-7/Cyr61 cells are tumorigenic in ovariectomized athymic nude mice. The tumors resemble human invasive carcinomas with increased vascularization and overexpression of vascular endothelial growth factor (VEGF). Our results demonstrate that Cyr61 is a tumor-promoting factor and a key regulator of breast cancer progression. This study provides evidence that Cyr61 is sufficient to induce E2-independence and antiestrogen-resistance, and to promote invasiveness in vitro, and to induce tumorigenesis in vivo, all of which are characteristics of an aggressive breast cancer phenotype.

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References

  • Babic AM, Chen CC, Lau LF . 1999 Mol. Cell. Biol. 19: 2958–2966

  • Babic AM, Kireeva ML, Kolesnikova TV, Lau LF . 1998 Proc. Natl. Acad. Sci. USA 95: 6355–6360

  • Brower ST, Cunningham JD, Tartter PI . 1999 Breast Cancer Roses DF (ed) New York: Churchill Livingstone pp 273–286

    Google Scholar 

  • Cardillo M, Tang C, Lupu R . 1995 Proc. AACR 36: 262

  • Cavailles V, Augereau P, Garcia M, Rochefort H . 1988 Nucleic Acids Res. 16: 1903–1919

  • Chen N, Chen CC, Lau LF . 2000 J. Biol. Chem. 275: 24953–24961

  • Chen CC, Mo FE, Lau LF . 2001 J. Biol. Chem. 276: 47329–47337

  • Frazier K, Williams S, Kothapalli D, Klapper H, Grotendorst GR . 1996 J. Invest. Dermatol. 107: 404–411

  • Gasparini G, Brooks PC, Biganzoli E, Vermeulen PB, Bonoldi E, Dirix LY, Ranieri G, Miceli R, Cheresh DA . 1998 Clin. Cancer Res. 4: 2625–2634

  • Govind AP, Thampan RV . 2001 J. Cell. Biochem. 80: 571–579

  • Guerra-Vladusic FK, Scott G, Weaver V, Vladusic EA, Tsai M-S, Benz CC, Lupu R . 1999 Int. J. Oncol. 15: 883–892

  • Hijazi M, Thompson EW, Tang C, Coopman P, Torry JA, Yang D, Mueller SC, Lupu R . 2000 Int. J. Oncol. 17: 629–641

  • Jedsadayanmata A, Chen CC, Kireeva ML, Lau LF, Lam SC . 1999 J. Biol. Chem. 274: 24321–24327

  • Kireeva ML, Lam SC, Lau LF . 1996a J. Biol. Chem. 273: 3090–3096

  • Kireeva ML, Mo F-E, Yang GP, Lau LF . 1996b Mol. Cell. Biol. 16: 1326–1334

  • Kireeva ML, Latinkic BV, Kolesnikova TV, Chen CC, Yang GP, Abler AS, Lau LF . 1997 Exp. Cell Res. 233: 63–77

  • Kolesnikova TV, Lau LF . 1998 Oncogene 16: 747–754

  • Lau LF, Lam SC . 1999 Exp. Cell Res. 246: 44–57

  • Lupu R, Cardillo M, Cho C, Harris L, Hijazi M, Perez C, Rosenberg K, Yang D, Tang C . 1996 Breast Cancer Res. Treat. 38: 57–66

  • Lupu R, Cardillo M, Harris L, Hijazi M, Rosenberg K . 1995 Semin. Cancer Biol. 6: 135–145

  • MacGregor JI, Jordan VC . 1998 Pharmacol. Rev. 50: 151–196

  • Meyer T, Marshall JF, Hart IR . 1998 Br. J. Cancer 77: 530–536

  • Nardulli AM, Greene CL, O'Malley BW, Katzenellenbogen BS . 1988 Endocrinol. 122: 935–944

  • O'Brien TP, Lau LF . 1992 Cell Growth Differ. 3: 645–654

  • Pratt SE, Pollak MN . 1993 Cancer Res. 53: 5193–5198

  • Read LS, Greene GL, Katzenellenbogen BS . 1989 Mol. Endocrinol. 3: 295–304

  • Saceda M, Grunt TW, Colomer R, Lippman ME, Lupu R, Martin MB . 1996 Endocrinol. 137: 4322–4330

  • Sampath D, Winneker RC, Zhang Z . 2001 Endocrinology 142: 2540–2548

  • Sommers CL, Thompson EW, Torri JA, Kemler R, Gelmann EP, Byers SW . 1991 Cell Growth Differ. 2: 365–372

  • Tang C, Grunt TW, Cho C, Weibel C, Perez C, Lupu R . 1996 Cancer Res. 56: 3350–3358

  • Tsai M-S, Hornby AE, Lakins J, Lupu R . 2000 Cancer Res. 60: 5603–5607

  • Tsai M-S, Bogart DF, Li P, Mehmi I, Lupu R . 2002 Oncogene 21: 964–973

  • Vladusic EA, Hornby AE, Guerra-Vladusic FK, Lakins J, Lupu R . 2000 Oncol. Rep. 7: 157–167

  • Weaver CA, Springer PA, Katzenellenbogen BS . 1988 Mol. Endocrinol. 2: 936–945

  • Xie D, Miller CW, O'Kelly J, Nakachi K, Sakashita A, Said JW, Gornbein J, Koeffler HP . 2001 J. Biol. Chem. 276: 14187–14194

  • Yang PG, Lau FL . 1991 Cell Growth Differ. 2: 351–357

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Acknowledgements

The authors thank Drs Judith Campisi and Nechama Smorodinsky for scientific discussion and Kevin Peet for editorial assistance. The authors would also like to thank Eddie Lo, Inderjit Mehmi, and Dr Ella Atlas for technical support during the course of this work. This work was supported by a grant from the National Institutes of Health (Contract No. DK49049), and the Department of Energy under Contract No. DE-AC03-76SF00098 (R Lupu), and the Breast Cancer Research Program Postdoctoral Traineeship from the Department of Defense (M-S Tsai).

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Correspondence to Ruth Lupu.

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Tsai, MS., Bogart, D., Castañeda, J. et al. Cyr61 promotes breast tumorigenesis and cancer progression. Oncogene 21, 8178–8185 (2002). https://doi.org/10.1038/sj.onc.1205682

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