Artículo

Carnevale, R.P.; Proietti, C.J.; Salatino, M.; Urtreger, A.; Peluffo, G.; Edwards, D.P.; Boonyaratanakornkit, V.; Charreau, E.H.; De Kier Joffé, E.B.; Schillaci, R.; Elizalde, P.V. "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" (2007) Molecular Endocrinology. 21(6):1335-1358
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Abstract:

Accumulating evidence indicates that progestins are involved in controlling mammary gland tumorigenesis. Here, we assessed the molecular mechanisms of progestin action in breast cancer models with different phenotypes. We examined C4HD cells, an estrogen (ER) and progesterone (PR) receptor-positive murine breast cancer model in which progestins exert sustained proliferative response, the LM3 murine metastatic mammary tumor cell line, which lacks PR and ER expression, and human PR null T47D-Y breast cancer cells. In addition to acting as a transcription factor, PR can also function as an activator of signaling pathways. To explore which of these two functions were involved in progestin responses, reconstitution experiments in the PR-negative models were performed with wild-type PR-B, with a DNA binding mutant C587A-PR, and with mutant PR-BmPro, which lacks the ability to activate cytoplasm signaling pathways. We found that in a cell context either ER-positive or -negative, progestins induced cell growth and modulation of matrix metalloproteinases-9 (MMP-9) and -2 (MMP-2), and urokinase-type plasminogen activator (uPA) activities, via MAPK and phosphatidylinositol 3-kinase/Akt pathways, in cells expressing wildtype PR-B or DNA binding mutant C587A-PR. In contrast, in cells expressing mutant PR-BmPro, progestins did not induce growth. We also found that unliganded PR expression conferred breast cancer cells an in vitro less proliferative phenotype, as compared with cells lacking PR expression. Modulation of this behavior occurred when PR was functioning either as transcription factor or as signaling activator. Finally, we for the first time demonstrated that progestins favor development of breast tumor metastasis via PR function as activator of signaling pathways. Our present findings provide mechanistic support to the design of a novel therapeutic intervention in PR-positive breast tumors involving blockage of PR capacity to activate cytoplasmic signaling. Copyright © 2007 by The Endocrine Society.

Registro:

Documento: Artículo
Título: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
Autor:Carnevale, R.P.; Proietti, C.J.; Salatino, M.; Urtreger, A.; Peluffo, G.; Edwards, D.P.; Boonyaratanakornkit, V.; Charreau, E.H.; De Kier Joffé, E.B.; Schillaci, R.; Elizalde, P.V.
Filiación:Instituto de Biología Y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas Y Técnicas, Buenos Aires C1428ADN, Argentina
Institute of Oncology Angel H. Roffo, University of Buenos Aires, Research Area, C1417DTB Buenos Aires, Argentina
Department of Molecular and Cellular Biology and Pathology, Baylor College of Medicine, Houston, TX 77030, United States
Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología Y Medicina Experimental (IBYME), Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
Palabras clave:DNA binding protein; estrogen receptor; gelatinase A; gelatinase B; gestagen; mitogen activated protein kinase; mutant protein; phosphatidylinositol 3 kinase; progesterone receptor; protein kinase B; transcription factor; urokinase; animal cell; animal experiment; animal model; article; breast cancer; breast carcinogenesis; cancer cell culture; cancer model; cell growth; cell proliferation; controlled study; cytoplasm; enzyme activation; female; hormonal regulation; hormone response; human; human cell; metastasis; modulation; mouse; nonhuman; null allele; phenotype; priority journal; protein function; signal transduction; wild type; 1-Phosphatidylinositol 3-Kinase; Animals; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cytoplasm; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mitogen-Activated Protein Kinase Kinases; Neoplasm Metastasis; Peptide Hydrolases; Progestins; Receptors, Progesterone; Signal Transduction; Urinary Plasminogen Activator; Murinae
Año:2007
Volumen:21
Número:6
Página de inicio:1335
Página de fin:1358
DOI: http://dx.doi.org/10.1210/me.2006-0304
Título revista:Molecular Endocrinology
Título revista abreviado:Mol. Endocrinol.
ISSN:08888809
CODEN:MOENE
CAS:gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; mitogen activated protein kinase, 142243-02-5; phosphatidylinositol 3 kinase, 115926-52-8; protein kinase B, 148640-14-6; urokinase, 139639-24-0; 1-Phosphatidylinositol 3-Kinase, EC 2.7.1.137; Matrix Metalloproteinase 2, EC 3.4.24.24; Matrix Metalloproteinase 9, EC 3.4.24.35; Mitogen-Activated Protein Kinase Kinases, EC 2.7.1.-; Peptide Hydrolases, EC 3.4.-; Progestins; Receptors, Progesterone; Urinary Plasminogen Activator, EC 3.4.21.73
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08888809_v21_n6_p1335_Carnevale

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Citas:

---------- APA ----------
Carnevale, R.P., Proietti, C.J., Salatino, M., Urtreger, A., Peluffo, G., Edwards, D.P., Boonyaratanakornkit, V.,..., Elizalde, P.V. (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. Molecular Endocrinology, 21(6), 1335-1358.
http://dx.doi.org/10.1210/me.2006-0304
---------- CHICAGO ----------
Carnevale, R.P., Proietti, C.J., Salatino, M., Urtreger, A., Peluffo, G., Edwards, D.P., et al. "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" . Molecular Endocrinology 21, no. 6 (2007) : 1335-1358.
http://dx.doi.org/10.1210/me.2006-0304
---------- MLA ----------
Carnevale, R.P., Proietti, C.J., Salatino, M., Urtreger, A., Peluffo, G., Edwards, D.P., et al. "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" . Molecular Endocrinology, vol. 21, no. 6, 2007, pp. 1335-1358.
http://dx.doi.org/10.1210/me.2006-0304
---------- VANCOUVER ----------
Carnevale, R.P., Proietti, C.J., Salatino, M., Urtreger, A., Peluffo, G., Edwards, D.P., et al. 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. 2007;21(6):1335-1358.
http://dx.doi.org/10.1210/me.2006-0304