Skip to main content

Advertisement

SpringerLink
Log in

Classical membrane progesterone receptors in murine mammary carcinomas: agonistic effects of progestins and RU-486 mediating rapid non-genomic effects

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

In this article, we demonstrate the expression of functional progesterone binding sites at the cell membrane in murine mammary carcinomas that are stimulated by progestins and inhibited by antiprogestins. Using confocal immunofluorescence, ligand binding and cell compartment-specific western blots, we were able to identify the presence of the classical progesterone receptors. Medroxyprogesterone acetate (MPA) and RU-486 (1 × 10−11 and 1 × 10−8 M) behaved as agonists activating extracellular signal-regulated kinases (ERKs) and progestin-regulated proteins, except for Cyclin D1 and Tissue factor which failed to increase with 1 × 10−8 M RU-486, an experimental condition that allows PR to bind DNA. These results predicted a full agonist effect at low concentrations of RU-486. Accordingly, at concentrations lower than 1 × 10−11 M, RU-486 increased cell proliferation in vitro. This effect was abolished by incubation with the ERK kinase inhibitor PD 98059 or by OH-tamoxifen. In vivo, at a daily dose of 1.2 μg/kg body weight RU-486 increased tumor growth, whereas at 12 mg/kg induces tumor regression. Our results indicate that low concentrations of MPA and RU-486 induce similar agonistic non-genomic effects, whereas RU-486 at higher concentrations may inhibit cell proliferation by genomic-induced effects. This suggests that RU-486 should be therapeutically administered at doses high enough to guarantee its genomic inhibitory effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

chFCS:

Steroid-stripped fetal calf serum

ERα:

ER alpha

MISS:

Membrane initiated steroid signaling

MPA:

Medroxyprogesterone acetate

mPR:

Membrane progesterone receptors

OH-Tam:

OH-Tamoxifen

PD:

PD 98059

Pg:

Progesterone

PI:

Propidium iodide

PR:

Progesterone receptor

PR-A:

PR isoform A

PR-B:

PR isoform B

s.c:

Subcutaneous

References

  1. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P (1995) The nuclear receptor superfamily: the second decade. Cell 83:835–839

    Article  PubMed  CAS  Google Scholar 

  2. Torchia J, Glass C, Rosenfeld MG (1998) Co-activators and co-repressors in the integration of transcriptional responses. Curr Opin Cell Biol 10:373–383

    Article  PubMed  CAS  Google Scholar 

  3. Bagchi MK, Tsai SY, Weigel NL, Tsai MJ, O’Malley BW (1990) Regulation of in vitro transcription by progesterone receptor. Characterization and kinetic studies. J Biol Chem 265:5129–5134

    PubMed  CAS  Google Scholar 

  4. Sutter-Dub MT (2002) Rapid non-genomic and genomic responses to progestogens, estrogens, and glucocorticoids in the endocrine pancreatic B cell, the adipocyte and other cell types. Steroids 67:77–93

    Article  PubMed  CAS  Google Scholar 

  5. Pietras RJ, Szego CM (1977) Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature 265:69–72

    Article  PubMed  CAS  Google Scholar 

  6. Cato AC, Nestl A, Mink S (2002) Rapid actions of steroid receptors in cellular signaling pathways. Sci STKE 138:RE9

    Google Scholar 

  7. Watson CS, Gametchu B (1999) Membrane-initiated steroid actions and the proteins that mediate them. Proc Soc Exp Biol Med 220:9–19

    Article  PubMed  CAS  Google Scholar 

  8. Song RX, Fan P, Yue W, Chen Y, Santen RJ (2006) Role of receptor complexes in the extranuclear actions of estrogen receptor alpha in breast cancer. Endocr Relat Cancer 13(Suppl 1):S3–S13

    Article  PubMed  CAS  Google Scholar 

  9. Ehring GR, Kerschbaum HH, Eder C, Neben AL, Fanger CM, Khoury RM, Negulescu PA, Cahalan MD (1998) A nongenomic mechanism for progesterone-mediated immunosuppression: inhibition of K+ channels, Ca2+ signaling, and gene expression in T lymphocytes. J Exp Med 188:1593–1602

    Article  PubMed  CAS  Google Scholar 

  10. Grazzini E, Guillon G, Mouillac B, Zingg HH (1998) Inhibition of oxytocin receptor function by direct binding of progesterone. Nature 392:509–512

    Article  PubMed  CAS  Google Scholar 

  11. Valera S, Ballivet M, Bertrand D (1992) Progesterone modulates a neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 89:9949–9953

    Article  PubMed  CAS  Google Scholar 

  12. McEwen BS (1991) Non-genomic and genomic effects of steroids on neural activity. Trends Pharmacol Sci 12:141–147

    Article  PubMed  CAS  Google Scholar 

  13. Krebs CJ, Jarvis ED, Chan J, Lydon JP, Ogawa S, Pfaff DW (2000) A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors. Proc Natl Acad Sci USA 97:12816–12821

    Article  PubMed  CAS  Google Scholar 

  14. Labombarda F, Gonzalez SL, Deniselle MC, Vinson GP, Schumacher M, De Nicola AF, Guennoun R (2003) Effects of injury and progesterone treatment on progesterone receptor and progesterone binding protein 25-Dx expression in the rat spinal cord. J Neurochem 87:902–913

    Article  PubMed  CAS  Google Scholar 

  15. Zhu Y, Bond J, Thomas P (2003) Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc Natl Acad Sci USA 100:2237–2242

    Article  PubMed  CAS  Google Scholar 

  16. Zhu Y, Rice CD, Pang Y, Pace M, Thomas P (2003) Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc Natl Acad Sci USA 100:2231–2236

    Article  PubMed  CAS  Google Scholar 

  17. Dressing GE, Thomas P (2007) Identification of membrane progestin receptors in human breast cancer cell lines and biopsies and their potential involvement in breast cancer. Steroids 72:111–116

    Article  PubMed  CAS  Google Scholar 

  18. Krietsch T, Fernandes MS, Kero J, Losel R, Heyens M, Lam EW, Huhtaniemi I, Brosens JJ, Gellersen B (2006) Human homologs of the putative G protein-coupled membrane progestin receptors (mPRalpha, beta, and gamma) localize to the endoplasmic reticulum and are not activated by progesterone. Mol Endocrinol 20:3146–3164

    Article  PubMed  CAS  Google Scholar 

  19. Thomas P, Pang Y, Dong J, Groenen P, Kelder J, de Vlieg J, Zhu Y, Tubbs C (2007) Steroid and G protein binding characteristics of the seatrout and human progestin membrane receptor alpha subtypes and their evolutionary origins. Endocrinology 148:705–718

    Article  PubMed  CAS  Google Scholar 

  20. Molinolo AA, Lanari C, Charreau EH, Sanjuan N, Pasqualini CD (1987) Mouse mammary tumors induced by medroxyprogesterone acetate: immunohistochemistry and hormonal receptors. J Natl Cancer Inst 79:1341–1350

    PubMed  CAS  Google Scholar 

  21. Helguero LA, Lamb C, Molinolo AA, Lanari C (2003) Evidence for two progesterone receptor binding sites in murine mammary carcinomas. J Steroid Biochem Mol Biol 84:9–14

    Article  PubMed  CAS  Google Scholar 

  22. Powell CE, Soto AM, Sonnenschein C (2001) Identification and characterization of membrane estrogen receptor from MCF7 estrogen-target cells. J Steroid Biochem Mol Biol 77:97–108

    Article  PubMed  CAS  Google Scholar 

  23. Razandi M, Pedram A, Greene GL, Levin ER (1999) Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells. Mol Endocrinol 13:307–319

    Article  PubMed  CAS  Google Scholar 

  24. Razandi M, Oh P, Pedram A, Schnitzer J, Levin ER (2002) ERs associate with and regulate the production of caveolin: implications for signaling and cellular actions. Mol Endocrinol 16:100–115

    Article  PubMed  CAS  Google Scholar 

  25. Welter BH, Hansen EL, Saner KJ, Wei Y, Price TM (2003) Membrane-bound progesterone receptor expression in human aortic endothelial cells. J Histochem Cytochem 51:1049–1055

    PubMed  CAS  Google Scholar 

  26. Younglai EV, Wu Y, Foster WG, Lobb DK, Price TM (2006) Binding of progesterone to cell surfaces of human granulosa-lutein cells. J Steroid Biochem Mol Biol 101:61–67

    Article  PubMed  CAS  Google Scholar 

  27. Luconi M, Francavilla F, Porazzi I, Macerola B, Forti G, Baldi E (2004) Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens. Steroids 69:553–559

    Article  PubMed  CAS  Google Scholar 

  28. Pedram A, Razandi M, Sainson RC, Kim JK, Hughes CC, Levin ER (2007) A conserved mechanism for steroid receptor translocation to the plasma membrane. J Biol Chem 282:22278–22288

    Article  PubMed  CAS  Google Scholar 

  29. Lanari C, Luthy I, Lamb CA, Fabris V, Pagano E, Helguero LA, Sanjuan N, Merani S, Molinolo AA (2001) Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins. Cancer Res 61:293–302

    PubMed  CAS  Google Scholar 

  30. Dran G, Luthy IA, Molinolo AA, Charreau EH, Pasqualini CD, Lanari C (1995) Effect of medroxyprogesterone acetate (MPA) and serum factors on cell proliferation in primary cultures of an MPA-induced mammary adenocarcinoma. Breast Cancer Res Treat 35:173–186

    Article  PubMed  CAS  Google Scholar 

  31. Fabris VT, Benavides F, Conti C, Merani S, Lanari C (2005) Cytogenetic findings, Trp53 mutations, and hormone responsiveness in a medroxyprogesterone acetate induced murine breast cancer model. Cancer Genet Cytogenet 161:130–139

    Article  PubMed  CAS  Google Scholar 

  32. Urtreger A, Ladeda V, Puricelli LI, Rivelli A, Vidal MC, Sacerdote de Lustig E, Bal de Kier Joffe E (1997) Modulation of fibronectin expression and proteolytic activity associated to the invasive and metastatic phenotype in two new murine mammary tumor cell lines. Int J Oncol 11:489–496

    CAS  Google Scholar 

  33. Clemm DL, Sherman L, Boonyaratanakornkit V, Schrader WT, Weigel NL, Edwards DP (2000) Differential hormone-dependent phosphorylation of progesterone receptor A and B forms revealed by a phosphoserine site-specific monoclonal antibody. Mol Endocrinol 14:52–65

    Article  PubMed  CAS  Google Scholar 

  34. Lowry OH, Rosebrough NJ, Farr AL (1951) Protein measurements with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  35. Kampa M, Nifli AP, Charalampopoulos I, Alexaki VI, Theodoropoulos PA, Stathopoulos EN, Gravanis A, Castanas E (2005) Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis. Exp Cell Res 307:41–51

    Article  PubMed  CAS  Google Scholar 

  36. Lamb CA, Helguero LA, Giulianelli S, Soldati R, Vanzulli SI, Molinolo A, Lanari C (2005) Antisense oligonucleotides targeting the progesterone receptor inhibit hormone-independent breast cancer growth in mice. Breast Cancer Res 7:R1111–R1121

    Article  PubMed  CAS  Google Scholar 

  37. Lamb C, Simian M, Molinolo A, Pazos P, Lanari C (1999) Regulation of cell growth of a progestin-dependent murine mammary carcinoma in vitro: progesterone receptor involvement in serum or growth factor-induced cell proliferation. J Steroid Biochem Mol Biol 70:133–142

    Article  PubMed  CAS  Google Scholar 

  38. Giulianelli S, Cerliani JP, Lamb CA, Fabris VT, Bottino MC, Gorostiaga MA, Novaro V, Gongora A, Baldi A, Molinolo A, Lanari C (2008) Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: a role for the FGF-2/FGFR-2 axis. Int J Cancer 123:2518–2531

    Article  PubMed  CAS  Google Scholar 

  39. Vanzulli SI, Soldati R, Meiss R, Colombo L, Molinolo AA, Lanari C (2005) Estrogen or antiprogestin treatment induces complete regression of pulmonary and axillary metastases in an experimental model of breast cancer progression. Carcinogenesis 26:1055–1063

    Article  PubMed  CAS  Google Scholar 

  40. Lanari C, Lamb CA, Fabris VT, Helguero LA, Soldati R, Bottino MC, Giulianelli S, Cerliani JP, Wargon V, Molinolo A (2009) The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer. Endocr Relat Cancer 16:333–350

    Article  PubMed  CAS  Google Scholar 

  41. Helguero LA, Viegas M, Asaithamby A, Shyamala G, Lanari C, Molinolo AA (2003) Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment. Breast Cancer Res Treat 79:379–390

    Article  PubMed  CAS  Google Scholar 

  42. Wargon V, Helguero LA, Bolado J, Rojas P, Novaro V, Molinolo A, Lanari C (2009) Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas. Breast Cancer Res Treat 116:449–460

    Article  PubMed  CAS  Google Scholar 

  43. Zhang Z, Maier B, Santen RJ, Song RX (2002) Membrane association of estrogen receptor alpha mediates estrogen effect on MAPK activation. Biochem Biophys Res Commun 294:926–933

    Article  PubMed  CAS  Google Scholar 

  44. Kousteni S, Bellido T, Plotkin LI, O’Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC (2001) Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104:719–730

    PubMed  CAS  Google Scholar 

  45. Qiu M, Olsen A, Faivre E, Horwitz KB, Lange CA (2003) Mitogen activated protein kinase regulates nuclear association of human progesterone receptors. Mol Endocrinol 17:628–642

    Article  PubMed  CAS  Google Scholar 

  46. Balana ME, Lupu R, Labriola L, Charreau EH, Elizalde PV (1999) Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas. Oncogene 18:6370–6379

    Article  PubMed  CAS  Google Scholar 

  47. Carbajal L, Deng J, Dressing GE, Hagan CR, Lange CA, Hammes SR (2009) Meeting review: extra-nuclear steroid receptors-integration with multiple signaling pathways. Steroids 74:551–554

    Article  PubMed  CAS  Google Scholar 

  48. Quiles I, Millan-Arino L, Subtil-Rodriguez A, Minana B, Spinedi N, Ballare C, Beato M, Jordan A (2009) Mutational analysis of progesterone receptor functional domains in stable cell lines delineates sets of genes regulated by different mechanisms. Mol Endocrinol 23:809–826

    Article  PubMed  CAS  Google Scholar 

  49. Marino M, Ascenzi P, Acconcia F (2006) S-Palmitoylation modulates estrogen receptor alpha localization and functions. Steroids 71:298–303

    Article  PubMed  CAS  Google Scholar 

  50. Salatino M, Beguelin W, Peters MG, Carnevale R, Proietti CJ, Galigniana MD, Vedoy CG, Schillaci R, Charreau EH, Sogayar MC, Elizalde PV (2006) Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation. Oncogene 25:7723–7739

    Article  PubMed  CAS  Google Scholar 

  51. Karteris E, Zervou S, Pang Y, Dong J, Hillhouse EW, Randeva HS, Thomas P (2006) Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term. Mol Endocrinol 20:1519–1534

    Article  PubMed  CAS  Google Scholar 

  52. Bullock LP, Barthe PL, Mowszowicz I, Orth DN, Bardin CW (1975) The effect of progestins on submaxillary gland epidermal growth factor: demonstration of androgenic, synandrogenic and antiandrogenic actions. Endocrinology 97:189–195

    Article  PubMed  CAS  Google Scholar 

  53. Kontula K, Paavonen T, Luukkainen T, Andersson LC (1983) Binding of progestins to the glucocorticoid receptor. Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes. Biochem Pharmacol 32:1511–1518

    Article  PubMed  CAS  Google Scholar 

  54. Montecchia MF, Lamb C, Molinolo AA, Luthy IA, Pazos P, Charreau E, Vanzulli S, Lanari C (1999) Progesterone receptor involvement in independent tumor growth in MPA-induced murine mammary adenocarcinomas. J Steroid Biochem Mol Biol 68:11–21

    Article  PubMed  CAS  Google Scholar 

  55. Horwitz KB, Tung L, Takimoto GS (1996) Novel mechanisms of antiprogestin action. Acta Oncol 35:129–140

    Article  PubMed  CAS  Google Scholar 

  56. Horwitz KB (1992) The molecular biology of RU486. Is there a role for antiprogestins in the treatment of breast cancer? Endocr Rev 13:146–163

    PubMed  CAS  Google Scholar 

  57. Labriola L, Salatino M, Proietti CJ, Pecci A, Coso OA, Kornblihtt AR, Charreau EH, Elizalde PV (2003) Heregulin induces transcriptional activation of the progesterone receptor by a mechanism that requires functional ErbB-2 and mitogen-activated protein kinase activation in breast cancer cells. Mol Cell Biol 23:1095–1111

    Article  PubMed  CAS  Google Scholar 

  58. Carnevale RP, Proietti CJ, Salatino M, Urtreger A, Peluffo G, Edwards DP, Boonyaratanakornkit V, Charreau EH, Bal de Kier JE, Schillaci R, Elizalde PV (2007) Progestin effects on breast cancer cell proliferation, proteases activation, and in vivo development of metastatic phenotype all depend on progesterone receptor capacity to activate cytoplasmic signaling pathways. Mol Endocrinol 21:1335–1358

    Article  PubMed  CAS  Google Scholar 

  59. Skildum A, Faivre E, Lange CA (2005) Progesterone receptors induce cell cycle progression via activation of mitogen-activated protein kinases. Mol Endocrinol 19:327–339

    Article  PubMed  CAS  Google Scholar 

  60. Arruvito L, Giulianelli S, Flores AC, Paladino N, Barboza M, Lanari C, Fainboim L (2008) NK cells expressing a progesterone receptor are susceptible to progesterone-induced apoptosis. J Immunol 180:5746–5753

    PubMed  CAS  Google Scholar 

  61. Park JI, Strock CJ, Ball DW, Nelkin BD (2003) The Ras/Raf/MEK/extracellular signal-regulated kinase pathway induces autocrine-paracrine growth inhibition via the leukemia inhibitory factor/JAK/STAT pathway. Mol Cell Biol 23:543–554

    Article  PubMed  CAS  Google Scholar 

  62. Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80:179–185

    Article  PubMed  CAS  Google Scholar 

  63. Murphy LO, Blenis J (2006) MAPK signal specificity: the right place at the right time. Trends Biochem Sci 31:268–275

    Article  PubMed  CAS  Google Scholar 

  64. Leonhardt SA, Boonyaratanakornkit V, Edwards DP (2003) Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids 68:761–770

    Article  PubMed  CAS  Google Scholar 

  65. Rowan BG, O’Malley BW (2000) Progesterone receptor coactivators. Steroids 65:545–549

    Article  PubMed  CAS  Google Scholar 

  66. Dressing GE, Hagan CR, Knutson TP, Daniel AR, Lange CA (2009) Progesterone receptors act as sensors for mitogenic protein kinases in breast cancer models. Endocr Relat Cancer 16:351–361

    Article  PubMed  CAS  Google Scholar 

  67. Kato S, Pinto M, Carvajal A, Espinoza N, Monso C, Sadarangani A, Villalon M, Brosens JJ, White JO, Richer JK, Horwitz KB, Owen GI (2005) Progesterone increases tissue factor gene expression, procoagulant activity, and invasion in the breast cancer cell line ZR-75-1. J Clin Endocrinol Metab 90:1181–1188

    Article  PubMed  CAS  Google Scholar 

  68. Owen GI, Richer JK, Tung L, Takimoto G, Horwitz KB (1998) Progesterone regulates transcription of the p21(WAF1) cyclin-dependent kinase inhibitor gene through Sp1 and CBP/p300. J Biol Chem 273:10696–10701

    Article  PubMed  CAS  Google Scholar 

  69. Cicatiello L, Addeo R, Sasso A, Altucci L, Petrizzi VB, Borgo R, Cancemi M, Caporali S, Caristi S, Scafoglio C, Teti D, Bresciani F, Perillo B, Weisz A (2004) Estrogens and progesterone promote persistent CCND1 gene activation during G1 by inducing transcriptional derepression via c-Jun/c-Fos/estrogen receptor (progesterone receptor) complex assembly to a distal regulatory element and recruitment of cyclin D1 to its own gene promoter. Mol Cell Biol 24:7260–7274

    Article  PubMed  CAS  Google Scholar 

  70. Lydon JP, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CA Jr, Shyamala G, Conneely OM, O’Malley BW (1995) Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev 9:2266–2278

    Article  PubMed  CAS  Google Scholar 

  71. Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ, Weinberg RA (1995) Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82:621–630

    Article  PubMed  CAS  Google Scholar 

  72. Boonyaratanakornkit V, Bi Y, Rudd M, Edwards DP (2008) The role and mechanism of progesterone receptor activation of extra-nuclear signaling pathways in regulating gene transcription and cell cycle progression. Steroids 73:922–928

    Article  PubMed  CAS  Google Scholar 

  73. Faivre EJ, Daniel AR, Hillard CJ, Lange CA (2008) Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol 22:823–837

    Article  PubMed  CAS  Google Scholar 

  74. Hoffman B, Liebermann DA (2008) Apoptotic signaling by c-MYC. Oncogene 27:6462–6472

    Article  PubMed  CAS  Google Scholar 

  75. Dressing GE, Lange CA (2009) Integrated actions of progesterone receptor and cell cycle machinery regulate breast cancer cell proliferation. Steroids 74:573–576

    Article  PubMed  CAS  Google Scholar 

  76. Faivre EJ, Lange CA (2007) Progesterone receptors upregulate Wnt-1 to induce epidermal growth factor receptor transactivation and c-Src-dependent sustained activation of Erk1/2 mitogen-activated protein kinase in breast cancer cells. Mol Cell Biol 27:466–480

    Article  PubMed  CAS  Google Scholar 

  77. Klijn JG, Setyono-Han B, Foekens JA (2000) Progesterone antagonists and progesterone receptor modulators in the treatment of breast cancer. Steroids 65:825–830

    Article  PubMed  CAS  Google Scholar 

  78. Gaddy VT, Barrett JT, Delk JN, Kallab AM, Porter AG, Schoenlein PV (2004) Mifepristone induces growth arrest, caspase activation, and apoptosis of estrogen receptor-expressing, antiestrogen-resistant breast cancer cells. Clin Cancer Res 10:5215–5225

    Article  PubMed  CAS  Google Scholar 

  79. Moore MR (2004) A rationale for inhibiting progesterone-related pathways to combat breast cancer. Curr Cancer Drug Targets 4:183–189

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Fundación Sales, ANPCyT (PICT 07-932 and PICT 05-38302), CONICET (PIP 5351). Drs. Gutkind, Amornphimoltham and Molinolo are supported by the Intramural Research Program of the Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD. We are very grateful to Dr. Elisa Bal de Kier Joffe for providing LM3 cells, to Julieta Bolado and to Pablo Do Campo for excellent technical assistance, and to Laboratorios Craveri, Buenos Aires for providing MPA depot and to Bayer Schering Pharma AG for the ZK230211. We also wish to thank Avon Foundation for an AACR travel award to MC Bottino and the UICC for an ICRETT fellowship to MC Bottino.

Conflict of interest statement

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas—CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina

    María Cecilia Bottino, Juan Pablo Cerliani, Paola Rojas, Sebastián Giulianelli, Rocío Soldati, Carolina Mondillo, María Alicia Gorostiaga & Claudia Lanari

  2. Laboratorio de Hormonas y Cáncer, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas—CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina

    Isabel A. Lüthy

  3. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

    Omar P. Pignataro & Juan Carlos Calvo

  4. Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research National Institutes of Health, Bethesda, MD, USA

    J. Silvio Gutkind,  Panomwat Amornphimoltham & Alfredo A. Molinolo

Authors
  1. María Cecilia Bottino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan Pablo Cerliani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paola Rojas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sebastián Giulianelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rocío Soldati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carolina Mondillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. María Alicia Gorostiaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Omar P. Pignataro
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Juan Carlos Calvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. Silvio Gutkind
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Panomwat Amornphimoltham
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alfredo A. Molinolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Isabel A. Lüthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Claudia Lanari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudia Lanari.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Non-linear regression analysis of Rh6G-CB7 titration curve (JPEG 74 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bottino, M.C., Cerliani, J.P., Rojas, P. et al. Classical membrane progesterone receptors in murine mammary carcinomas: agonistic effects of progestins and RU-486 mediating rapid non-genomic effects. Breast Cancer Res Treat 126, 621–636 (2011). https://doi.org/10.1007/s10549-010-0971-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-010-0971-3

Keywords

Search

Navigation