title: Relationship between RUNX1 and AXIN1 in ER-negative versus ER-positive Breast Cancer.
abstract: RUNX1 plays opposing roles in breast cancer: a tumor suppressor in estrogen receptor-positive (ER+) disease and an oncogenic role in ER-negative (ER-) tumors. Potentially mediating the former, we have recently reported that RUNX1 prevents estrogen-driven suppression of the mRNA encoding the tumor suppressor AXIN1. Accordingly, AXIN1 protein expression was diminished upon RUNX1 silencing in ER+breast cancer cells and was positively correlated with AXIN1 protein expression across tumors with high levels of ER. Here we report the surprising observation that RUNX1 and AXIN1 proteins are strongly correlated in ER-tumors as well. However, this correlation is not attributable to regulation of AXIN1 by RUNX1 or vice versa. The unexpected correlation between RUNX1, playing an oncogenic role in ER-breast cancer, and AXIN1, a well-established tumor suppressor hub, may be related to a high ratio between the expression of variant 2 and variant 1 (v2/v1) of AXIN1 in ER-compared with ER+breast cancer. Although both isoforms are similarly regulated by RUNX1 in estrogen-stimulated ER+breast cancer cells, the higher v2/v1 ratio in ER-disease is expected to weaken the tumor suppressor activity of AXIN1 in these tumors.
authors.affiliation: a Department of Medicine , Keck School of Medicine of the University of Southern California , Los Angeles , CA , USA.|b Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California , Los Angeles , CA , USA.
authors.forename: Nyam-Osor
authors.initials: NO
authors.lastname: Chimge
authors.affiliation: b Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California , Los Angeles , CA , USA.|c Department of Biochemistry and Molecular Biology , Keck School of Medicine of the University of Southern California , Los Angeles , CA , USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Ahmed-Alnassar
authors.affiliation: b Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California , Los Angeles , CA , USA.|c Department of Biochemistry and Molecular Biology , Keck School of Medicine of the University of Southern California , Los Angeles , CA , USA.|d Department of Orthopedic Surgery , Keck School of Medicine of the University of Southern California , Los Angeles , CA , USA.
authors.forename: Baruch
authors.initials: B
authors.lastname: Frenkel
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D050676:Core Binding Factor Alpha 2 Subunit; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen
keywords: AXIN1 alternative splicing; oncogene; tumor suppressor