Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy.
作者： Vanessa M. López-Ozuna , Ibrahim Y. Hachim , Mahmood Y. Hachim , Jean-Jacques Lebrun , Suhad Ali
DOI: 10.1038/SREP30934
关键词:
摘要: Triple negative breast cancer (TNBC) is a heterogeneous disease associated with poor clinical outcome and lack of targeted therapy. Here we show that prolactin (PRL) its signaling pathway serve as sub-classifier predictor pro-differentiation therapy in TNBC. Using immunohistochemistry various gene expression silica analyses observed receptor (PRLR) protein mRNA levels are down regulated TNBC cases. In addition, examining correlation PRLR metagenes subtypes (580 cases), found sub-classifies patients into new subgroup (TNBC-PRLR) characterized by epithelial-luminal differentiation. Importantly, PRL components individually (PRL, PRLR, Jak2 Stat5a), or signature able to predict significantly better survival outcomes. As hormone druggable target determined the biological role biology. Significantly, restoration/activation cells representative mesenchymal TNBC-PRLR subgroups led induction epithelial phenotype suppression tumorigenesis. Altogether, these results offer potential modalities for stratification development personalized based on activation.
nature.com
harvard.edu
omicsonline.org 参考文章(57)
Zhiyuan Hu, Cheng Fan, Daniel S Oh, JS Marron, Xiaping He, Bahjat F Qaqish, Chad Livasy, Lisa A Carey, Evangeline Reynolds, Lynn Dressler, Andrew Nobel, Joel Parker, Matthew G Ewend, Lynda R Sawyer, Junyuan Wu, Yudong Liu, Rita Nanda, Maria Tretiakova, Alejandra Ruiz Orrico, Donna Dreher, Juan P Palazzo, Laurent Perreard, Edward Nelson, Mary Mone, Heidi Hansen, Michael Mullins, John F Quackenbush, Matthew J Ellis, Olufunmilayo I Olopade, Philip S Bernard, Charles M Perou, The molecular portraits of breast tumors are conserved across microarray platforms BMC Genomics. ,vol. 7, pp. 96- 96 ,(2006) , 10.1186/1471-2164-7-96
Christopher J. Ormandy, Nadine Binart, Paul A. Kelly, Mammary gland development in prolactin receptor knockout mice. Journal of Mammary Gland Biology and Neoplasia. ,vol. 2, pp. 355- 364 ,(1997) , 10.1023/A:1026395229025
Tomohiro Yonezawa, Kuan-Hui (Ethan) Chen, Mrinal K. Ghosh, Lorena Rivera, Riva Dill, Lisa Ma, Pedro A. Villa, Mitsumori Kawaminami, Ameae M. Walker, Anti-metastatic outcome of isoform-specific prolactin receptor targeting in breast cancer Cancer Letters. ,vol. 366, pp. 84- 92 ,(2015) , 10.1016/J.CANLET.2015.06.010
Jennet M. Harvey, Gary M. Clark, C. Kent Osborne, D. Craig Allred, Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer Journal of Clinical Oncology. ,vol. 17, pp. 1474- 1474 ,(1999) , 10.1200/JCO.1999.17.5.1474
H Wennbo, M Gebre-Medhin, A Gritli-Linde, C Ohlsson, O G Isaksson, J Törnell, Activation of the prolactin receptor but not the growth hormone receptor is important for induction of mammary tumors in transgenic mice Journal of Clinical Investigation. ,vol. 100, pp. 2744- 2751 ,(1997) , 10.1172/JCI119820
Hannah Farmer, Nuala McCabe, Christopher J. Lord, Andrew N. J. Tutt, Damian A. Johnson, Tobias B. Richardson, Manuela Santarosa, Krystyna J. Dillon, Ian Hickson, Charlotte Knights, Niall M. B. Martin, Stephen P. Jackson, Graeme C. M. Smith, Alan Ashworth, Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Nature. ,vol. 434, pp. 917- 921 ,(2005) , 10.1038/NATURE03445
Samir Ali, Suhad Ali, Prolactin Receptor Regulates Stat5 Tyrosine Phosphorylation and Nuclear Translocation by Two Separate Pathways Journal of Biological Chemistry. ,vol. 273, pp. 7709- 7716 ,(1998) , 10.1074/JBC.273.13.7709
Pascal Jézéquel, Mario Campone, Wilfried Gouraud, Catherine Guérin-Charbonnel, Christophe Leux, Gabriel Ricolleau, Loïc Campion, bc-GenExMiner: an easy-to-use online platform for gene prognostic analyses in breast cancer Breast Cancer Research and Treatment. ,vol. 131, pp. 765- 775 ,(2012) , 10.1007/S10549-011-1457-7
S R Oakes, F G Robertson, J G Kench, M Gardiner-Garden, M P Wand, J E Green, C J Ormandy, Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions. Oncogene. ,vol. 26, pp. 543- 553 ,(2007) , 10.1038/SJ.ONC.1209838
Lothar Hennighausen, Gertraud W. Robinson, Information networks in the mammary gland Nature Reviews Molecular Cell Biology. ,vol. 6, pp. 715- 725 ,(2005) , 10.1038/NRM1714