title: RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptor α.
abstract: Transcription factor RUNX3 is inactivated in a number of malignancies, including breast cancer, and is suggested to function as a tumor suppressor. How RUNX3 functions as a tumor suppressor in breast cancer remains undefined. Here, we show that about 20% of female Runx3(+/-) mice spontaneously developed ductal carcinoma at an average age of 14.5 months. Additionally, RUNX3 inhibits the estrogen-dependent proliferation and transformation potential of ERα-positive MCF-7 breast cancer cells in liquid culture and in soft agar and suppresses the tumorigenicity of MCF-7 cells in severe combined immunodeficiency mice. Furthermore, RUNX3 inhibits ERα-dependent transactivation by reducing the stability of ERα. Consistent with its ability to regulate the levels of ERα, expression of RUNX3 inversely correlates with the expression of ERα in breast cancer cell lines, human breast cancer tissues and Runx3(+/-) mouse mammary tumors. By destabilizing ERα, RUNX3 acts as a novel tumor suppressor in breast cancer.
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: B
authors.initials: B
authors.lastname: Huang
authors.forename: Z
authors.initials: Z
authors.lastname: Qu
authors.forename: C W
authors.initials: CW
authors.lastname: Ong
authors.forename: Y-H N
authors.initials: YH
authors.lastname: Tsang
authors.forename: G
authors.initials: G
authors.lastname: Xiao
authors.forename: D
authors.initials: D
authors.lastname: Shapiro
authors.forename: M
authors.initials: M
authors.lastname: Salto-Tellez
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: L-F
authors.initials: LF
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control*; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C493729:Runx3 protein, human; C493730:Runx3 protein, mouse; D025521:Tumor Suppressor Proteins; D046988:Proteasome Endopeptidase Complex