Grupo Kordon – IFIBYNE – CONICET

Area de estudio

Desarrollo normal y neoplásico de la glándula mamaria Mammary gland and breast cancer development

Dra. Edith Kordon
JEFA DE GRUPO / GROUP LEADER

Profesora Asociada, Departamento de Química Biológica, FCEN, UBA.
Investigadora Principal CONICET

Nuestro grupo busca determinar la relevancia de diversos factores que participan en el desarrollo del cáncer de mama tratando de identificar cuál es su rol fisiológico en el desarrollo y funcionamiento de la glándula mamaria normal. Actualmente, estamos centrados en la actividad y regulación de factores que se expresan en poblaciones de células progenitoras mamarias y tienen un impacto significativo en el desarrollo tumoral. En este contexto general, nuestro trabajo actual está centrado en dos líneas particulares:

Our group seeks to determine the relevance of various factors that participate in the development of breast cancer, trying to identify their physiological role in the development and functioning of the normal mammary gland. Currently, we are focused on the activity and regulation of factors that are expressed in populations of mammary progenitor cells and have a significant impact on tumor development. In this general context, our current work is focused on two specific lines:

Regulación de la expresión y actividad de la tristetraprolina (TTP) en la mama normal y neoplásica // Tristetraprolin (TTP) expression and activity regulation in normal and neoplastic mammary gland

La tristetraprolina (TTP) es una proteína capaz de inducir la degradación de RNAs mensajeros de proteínas involucradas en procesos inflamatorios y en la invasividad de células tumorales. Nosotros hallamos que la expression de TTP está fuertemente inhibida en el cancer mamario, particularmente en los más invasivos. Además, encontramos que la expresión de TTP es decisiva para la supervivencia de células tanto diferenciadas como progenitoras del tejido mamario.Nuestros objetivos actuales están centrados en determinar los mecanismos asociados a la inhibición de su expresión en el desarrollo tumoral.

Tristetraprolin (TTP) is a protein capable of inducing the degradation of messenger RNAs of proteins involved in inflammatory processes and in the invasiveness of tumor cells. We found that TTP expression is strongly inhibited in breast cancer, particularly in the most invasive ones. Furthermore, we found that the expression of TTP is decisive for the survival of both differentiated and progenitor cells of breast tissue. Presently our aims are focused on determining the mechanisms associated with the inhibition of its expression in tumor development.

Regulación de la expresión y actividad de R-spondin3 (Rspo3) en la tumorigénesis mamaria // Espression and activity regulation of R-spondin3 (RSPO3) in mammary tumorigenesis

Hemos demostrado que la expression de Rspo3 es inducida durante la progresión de tumores mamarios inducidos por el virus del tumor mamario murino (MMTV). Más recientemente hallamos que Rspo3 es expresado por células basales progenitoras de la glándula mamaria normal y en cáncer de mama humano, fundamentalmente del subtipo basal. Esta proteína induce transición epitelio-mesenquimal y crecimiento tumoral in vivo. Nuestros objetivos actuales incluyen analizar los mecanismos de regulación de su expresión y estrategias para la inhibición de su actividad oncogénica.

We have shown that Rspo3 expression is induced during the progression of mammary tumors induced by murine mammary tumor virus (MMTV). More recently we found that Rspo3 is expressed by basal progenitor cells of the normal mammary gland and in human breast cancer, mainly of the basal subtype. This protein induces epithelial-mesenchymal transition and tumor growth in vivo. Our current goal include analyzing the mechanisms of regulation of its expression and strategies for the inhibition of its oncogenic activity.

actividad oncogénica.

Publicaciones

Last 6 years

Stedile M, Lara Montero A, García Solá ME, Goddio MV, Beckerman I, Bogni E, Ayre M, Naguila Z, Coso OA, Kordon E. Tristetraprolin promotes survival of mammary progenitor cells by restraining TNFa levels. Front Cell Dev Biol. 11:1265475. 2024, doi: 10.3389/fcell.2023.1265475.

Schere-Levy C; Suberbordes M, Ferri D, Ayre M, Gattelli A, Kordon E, Raimondi A, Walther T. Treatment with Angiotensin-(1-7) prevents development of oral papilloma induced in K-ras transgenic mice. Int J Mol Sci23(7), 3642; 2022, doi.org/10.3390/ijms23073642

Vallone SA, Solá MG, Schere-Levy C, Meiss RP, Hermida GN, Chodosh LA, Kordon E, Hynes NE, Gattelli A. Aberrant RET expression impacts on normal mammary gland post lactation transition enhancing cancer potential. Dis Model Mech 15(3), 2022, doi: 10.1242/dmm.049286.

Felcher CM, Bogni ES,Kordon E. IL-6 Cytokine Family: A Putative Target for Breast Cancer Prevention and Treatment. Int J Mol Sci 23(3):1809, 2022, doi:10.3390/ijms23031809.

Kordon E, Lanari C, Simian M. Buenos Aires Breast Cancer Symposium BA-BCS 2021: Tribute to Dr. Christiane Dosne Pasqualini in her 101 birthday, May, 17-21, 2021. Medicina (B Aires) 81 Suppl 1:1-47, 2021.

Kordon E, · Lanari C.· Mando P, · Novaro V, · Rossi M, · Simian M. The BA‑BCS 2021: An Initial “Trial” for Integrating Basic Science and Medical Progress on Breast Cancer in a Latin‑American Country. J Mammary Gland Biol Neoplasia26(3):227-234, 2021

44. van Amerongen R, Kordon E, Koledova Z. Connecting the Dots: Mammary Gland and Breast Cancer at Single Cell Resolution. J Mammary Gland Biol Neoplasia 26(1):1-2, 2021

43. García Solá ME, Stedile M, Beckerman I, Kordon E. An Integrative Single-cell Transcriptomic Atlas of the Post-natal Mouse Mammary Gland Allows Discovery of New Developmental Trajectories in the Luminal Compartment. J Mammary Gland Biol Neoplasia 26(1):29-42, 2021.

Canzoneri R, Naipauer J, Stedile M, Rodriguez Peña A, Lacunza E, Gandini NA, Curino AC, Facchinetti MM, Coso OA,Kordon E, Abba MC. Identification of an AP1-ZFP36 Regulatory Network Associated with Breast Cancer Prognosis. J Mammary Gland Biol Neoplasia 25(2):163-172, 2020.

Tocci JM, Felcher CM, García Solá ME,Kordon E. R-spondin-mediated WNT signaling potentiation in mammary and breast cancer development. IUBMB Life I72(8):1546-1559, 2020.

40. Grinman G, Careaga V, Wellberg E, Dansey MV, Kordon E, Anderson S, Maier M, Burton G., MacLean P., Rudolph M, Pecci A. Liver X Receptor α Activation Enhances Cholesterol Secretion in Lactating Mammary Epithelium. AJP Endocrinology and Metabolism 316(6):E1136-E1145,

39. Tocci JM, Felcher CM; García Solá ME, Goddio MV, Zimberlin MN, Rubinstein N, Srebrow A, Coso OA, Abba MC, Meiss RP, Kordon E. R-spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells. Cancer Res 78(16):4497-4511, 2018.

Gattelli A, García Solá ME, Roloff TC, Cardiff RD, Kordon E, Chodosh LA, Hynes NE. Chronic expression of wild-type Ret receptor in the mammary gland induces luminal tumors that are sensitive to Ret inhibition. Oncogene 37(29):4046-54, 2018

37. Goddio MV, Gattelli A, Tocci JM, Cuervo LP, Stedile M, Stumpo DJ, Hynes NE, Blackshear PJ, Meiss RP, Kordon E. Expression of the mRNA stability regulator Tristetraprolin is required for lactation maintenance in the mouse mammary gland. Oncotarget 9(9):8278-89, 2018.

Book chapters (last 6 years)

Burachik NB, Ortiz AL, Kordon EC. Discovery of BRCA Mutations: Historical Perspective of Its Scientific, Clinical and Social Impact. En BRCA1 and BRCA2 mutations-Diagnostic and Therapeutic Implication. Mani T. Valarmathi (Editor), 2023.DOI:10.5772/intechopen.108648.

Most relevant previous papers (5)

Goddio M., Gattelli A, Slomiansky V., Lacunza E., Gingerich T., Curino A., Facchinetti M., LaMarre J., Abba M. and Kordon E. Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein. Breast Cancer Res Treat 135(3):749-58, 2012.

Gattelli A., Zimberlin M., Castilla L. and Kordon E. Selection of early occurring mutations dictates hormone-independency progression in mouse mammary tumor lines. J Virol. 80: 11409–15, 2006.

Gattelli A., Cirio M., Quaglino A., Schere-Levy C., Martinez N., Binaghi M., Meiss RP., Castilla LH. and Kordon E. Progression of pregnancy-dependent mouse mammary tumors after long dormancy periods. involvement of wnt pathway activation. Cancer Res. 64: 5193-99, 2004.

Buggiano V., Schere-Levy C., Abe K., Vanzulli S., Piazzon I., Smith G.H. and Kordon E. Impairment of mammary lobular development induced by expression of TGFb1 under the control of WAP promoter does not suppress tumorigenesis in MMTV-infected transgenic mice. Int. J. Cancer 92: 568-76, 2001.

Kordon E. and Smith G.H. An entire functional mammary gland may comprise the progeny from a single cell. Development 125: 1921-30, 1998.