Hormonal Carcinogenesis

    The aim of our laboratory is to study the mechanisms involved in hormone dependent breast cancer growth. We have focused our studies investigating the role of progesterone receptors in tumor growth. These studies led us to propose that antiprogestins (drugs able to block progesterone receptor action) could be used as therapeutic tools in selected groups of breast cancer patients. 

      

           

Hormonal Carcinogenesis

  • Claudia Lanari Currículum Vitae

    Superior Investigator, CONICET

  • embers

     

    Researchers from CONICET

    Dr. Caroline A. Lamb, PhD (Adjunct Researcher)

    Dr. Victoria Fabris, PhD (Adjunct Researcher)

    Dr. Paola Rojas, PhD (Assistant Researcher)

    Dr. Cecilia Pérez Piñero, PhD (Assistant Researcher)

    Dr. Sebastián Giulianelli, PhD (Assistant Researcher, CEMPAT)

      

    Principal Technician CONICET:

    Dr. María Gorostiaga (PhD)

     

    Fellows

    PhD Gonzalo Sequeira (Postdoctoral, CONICET)

    MD Marcos Liguori (Doctoral PID Agencia)

    María Florencia Abascal (Doctoral CONICET)

    Virginia Figueroa (Doctoral, CONICET)

    Gabriela Pataccini (Doctoral CONICET)

    Andrés Elía (Doctoral CONICET)

    Ayelén Rubin (Bachelor student, Biology)

    Sol Rodríguez (Bachelor student, Biology)

    Marina  Ayre (Bachelor student, Biology)

     

    Clinical Collaborators, Hospital “Magdalena V. de Martínez of General Pacheco”:

    Hugo Gass, MD

    Paula Martínez Vázquez, MD

    Pedro González, MD

    Javier Buruchaga, MD

     

    Extramural collaborators

    Alfredo A. Molinolo, MD, PhD UCSD, Moores Cancer Center; La Jolla, USA)

    Silvia I. Vanzulli, MD, PhD (Academia Nacional de Medicina, Buenos Aires, Argentina)

    Martín Abba, PhD (University of La Plata, La Plata, Argentina)

    Stephan Hewitt, MD, PhD (NCI, NIH, Bethesda, USA)

    Charles Perou, PhD (University of North Carolina; Chapell Hill, USA)

Hormonal carcinogenesis

           In 1984 we developed a murine experimental model of breast cancer that we have used to characterize different aspects of cancer progression during the past thirty years. These tumors share many features with human breast cancers as they: express estrogen (ER) and progesterone receptors (PR), transit through different stages of hormone dependency and display a ductal histology. We have shared this model with several research groups from IBYME and other Institutes. The different cell lines developed are being used by other researchers, mainly in Canada, for testing ER- binding compounds which might be used for the early detection of metastasis.

             This experimental model was originated by the continuous administration of medroxyprogesterone acetate (MPA) to BALB/c mice. Our findings contributed to the reclassification of MPA as an agent with possible carcinogenic effects in animals (IARC).

             In the last 20 years our main interest focused in studying the role of PR in mammary tumor growth and we demonstrated that together with ER they play a significant role regulating tumor growth. We demonstrated that factors from the tumor microenvironment such as FGF2 were able to activate PR in a ligand-independent manner, explaining thus the hormone independent pattern of tumor growth of a subgroup of mammary tumors.

             In addition, we studied the differential role of the two PR isoforms: A and B, showing that only tumors with higher levels of PRA than PRB are inhibited by antiprogestin treatment. Tumors that acquire antiprogestin resistance lose the expression of PRA. This prompted us to postulate that tumors will respond to antiprogestin treatment according to their PR isoform ratio.

             This study, which began in murine preclinical models and that, was later confirmed in human breast cancer cell lines and ex vivo cultures of breast cancers, prompted us to design a clinical trial for the neoadjuvant treatment of selected breast cancer patients with an antiprogestin.

Since 2012
  1. Lanari C, Wargon V, Rojas P MolinoloAA. Antiprogestins in breast cancer treatment. Are we ready? Endocrine Related Cancer, 2012 May 3;19(3):R35-50. Print 2012. (IF: 5.2)
  2. Fabris VT, Lodillinsky L, Pampena MB, Belgorosky D, Lanari C and Eiján A.M. Cytogenetic characterization of the murine bladder cancer model MB49 and the derived invasive line MB49-I. Cancer Genet. 2012 Apr;205(4):168-76 (IF: 1.91)
  3. Giulianelli S, Vaqué JP, Soldati R, Wargon V, Vanzulli SI, Martins R, Zeitlin E, Molinolo AA, Helguero LA, Lamb CA, Gutkind JS and Lanari C. Estrogen receptor alpha mediates progestin-induced mammary tumor growth by interacting with progesterone receptors at the Cyclin D1/MYC promoters”, Cancer Res. 2012 May 1;72(9):2416-27. (IF 8.65).
  4. Giulianelli SG, Vaqué JP, Wargon V, Soldati R, Vanzulli SI, Martins R, Zeitlin E, Helguero L, Lamb CA, Molinolo AA, Gutkind JS, Lanari C. El receptor de estrógenos alfa como mediador del efecto proliferativo de progestágenos en cáncer de mama. Medicina (B Aires) 2012; 72: 315-320.
  5. Cotrim CZ; Fabris V, Doria ML; Lindberg K; Gustafsson J, Amado F; Lanari C and Helguero LA. Estrogen receptor beta growth inhibitory effects are repressed through activation of MAPK and PI3K signalling in mammary epithelial and breast cancer cells. Oncogene 2013 May 9;32(19):2390-402 doi:10.1038/onc.2012.261 (IF: 8.55)
  6. Sebastián Giulianelli, Alfredo Molinolo and Claudia Lanari. Targeting progesterone receptors in breast cancer. In Gerald Litwack, editors: Hormones and Breast Cancer, Vol 93, VH, UK: Academic Press, 2013, pp. 161-184.
  7. Pontillo C, Rojas P, Chiappini F, Sequeira G, Cocca C, Crocci M, Colombo L, Lanari C, Kleiman de Pisarev D, Randi A. Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models. Toxicology and Applied Pharmacology 2013 May 1;268(3):331-42. doi: 10.1016/j.taap.2013.02.007. Epub 2013 Feb 24 (IF: 3.63).
  8. Sahores A, Luque GM, Wargon V, May M, Molinolo A, Becu-Villalobos D, Lanari C, Lamb CA. Novel, Low Cost, Highly Effective, Handmade Steroid Pellets for Experimental Studies Plos One, 2013 May 15;8(5):e64049. doi: 10.1371/journal.pone.0064049. Print 2013 (IF: 3.53).
  9. Caroline Lamb, Ana Sahores, John Lydon, Alfredo Molinolo and Claudia Lanari. Role for Mifepristone in breast cáncer. Chapter 3. En Mifepristone. Pharmacology, Medical Use and potential side effects, Editor Ariana Moore, Nova Biomedical, New York pages 51-70, 2014.
  10. Sequeira, G., Vanzulli, S. I., Rojas, P., Lamb, C., Colombo, L., May, M., Molinolo A, Novaro V. & Lanari, C. (2014). The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer. Oncotarget, 2014 May 30;5(10):3246-60 (IF: 6.35).
  11. Wargon V, Riggio M, Giulianelli S, Sequeira G, Rojas P, May M, Polo ML, Gorostiaga MA, Molinolo A, Novaro V, Lanari C. Breast carcinomas with differential PR isoform expression may respond to antiprogestins: an experimental approach. International Journal of Cancer 2015 Jun 1;136(11):2680-92. doi: 10.1002/ijc.29304. Epub 2014 Nov 12.
  12. Langle YV, Belgorosky D, Prack Mc Cormick B, Sahores A, Góngora A, Baldi A, Lanari C, Lamb C, Eiján AM. FGFR3 down-regulation is involved in BCG-induced bladder tumor growth inhibition. J Urol. 2016 Jan;195(1):188-97. doi: 10.1016/j.juro.2015.06.093.
  13. Polo ML, Riggio M, May M, Rodríguez MJ, Perrone MC, Stallings-Mann M, Kaen D, Frost M, Goetz M, Boughey J, Lanari C, Radisky D, Novaro V. Activation of PI3K/Akt/mTOR signaling in the tumor stroma drives endocrine therapy-dependent breast tumor regression. Oncotarget. 2015 Jun 8. Sep 8;6(26):22081-97
  14. May M, Mosto J, Vazquez PM, Gonzalez P, Rojas P, Gass H, Lanari C, Molinolo AA. Nuclear staining of fgfr-2/stat-5 and runx-2 in mucinous breast cancer. Exp Mol Pathol. 2015 Nov 6. 2016 Feb;100(1):39-44. doi: 10.1016/j.yexmp.2015.11.003.
  15. Gargiulo L, May M , Rivero EM, Copsel S , Lamb C , Lydon J , Davio C, Lanari C, Lüthy IA , Bruzzone A. A novel effect of β-adrenergic receptor on mammary branching morphogenesis and its possible implications in breast cancer. J of Mammary Gland Biol Neoplasia, Mar 22 (1): 43-57. doi: 10.1007/s10911-017-9371-1, 2017.
  16. Rojas PA, May M, Sequeira G, Elia A, Alvarez M, Martínez P Gonzalez P, Hewitt S, He X, Perou CM, Molinolo A , Gibbons L, Abba MC, Gass H and Lanari C. Progesterone receptor isoform ratio: A breast cancer prognostic and predictive factor for antiprogestin responsiveness. J Natl Cancer Inst Jul 1: 109 (7) doi: 10.1093/jnci/djw317. 2017
  17. Riggio M, Perrone C, May M, Polo ML, Rodriguez J, Abba M Lanari C, Novaro V. AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins" Scientific Reports, 13;7:44244. doi: 10.1038/srep44244, 2017.
  18. Fabris V, Abascal MF, Giulianelli S, May M, Sequeira GR, Jacobsen B, Lombès M, Han J, Tran L, Molinolo A and Lanari C. Isoform Specificity of Progesterone Receptor Antibodies. The Journal of Pathology: Clinical Research, in press 2017.
Awards

Avon Foundation to attend the Annual Meeting of the American Association for Cancer Reserch:

            2010 (Washington DC):      Sebastián Giulianelli

                                                Juan Pablo Cerliani.

            2011 (Orlando, FL):          Sebastián Giulianelli

                                                Victoria Wargon

                                                Tomás Guillardoy

                                                Marina Riggio

                                                María Laura Polo

 

            2013 (Washington DC):      María Laura Polo

                                                Ana Sahores 

Avon Foundation to attend the Meeting of Advances in Breast Cancer Research:

             2011 (San Francisco):       Sebastián Giulianelli

                                                Marina Riggio

 

             2013 (San Diego):           Gonzalo Sequeira

                                                Ana Sahores

                                                Tomás Guillardoy

Avon Foundation to attend the Meeting of San Antonio Breast Cancer Symposium:

 

             2010 (San Antonio):    Paola Rojas

             2012 (San Antonio):    Gonzalo Sequeira

 

International Academy of Pathology (IAP) to attend the Annual Meeting.

              2012 (Cape Town)     María May

 

Other awards (2010-2015):

2011. Barón Award. Lalcec “Interacción Estroma-Epitelio en la adquisición de la hormono independencia en carcinomas mamarios. Papel de los receptores de progesterona y de los receptores de los factores de crecimiento fibroblásticos”. Authors: Dr. Juan Pablo Cerliani, Lic. Tomas Guillardoy, Dra. María Alicia Gorostiaga, Dra. Caroline A. Lamb and Dra. Claudia Lanari.

2011. Eugenia Sacerdote de Lustig Award, CEDIQUIFA: RESISTENCIA CONSTITUTIVA Y ADQUIRIDA AL TRATAMIENTO HORMONAL DE CARCINOMAS MAMARIOS MURINOS, Victoria Wargon, Virginia Novaro, Sebastian Giulianelli, María Gorostiaga, Claudia Lanari.

2012. Cherny Award to the best presentation at the  Annual SAIC Meeting: S. Giulianelli (PhD).

2012 . “Profesor Emanuel Levin” award to the best poster presentation in breast cáncer: Antiprogestágenos en cáncer de mama: hacia una terapia personalizada. Autores: Gass H, May M, Sequeira G, Martínez P, Gonzalez P. Rojas P, Lanari C. XV Congreso Argentino de Cancerología; 9-11 August, 2012.

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