title: Pttg1 inhibits TGFβ signaling in breast cancer cells to promote their growth.
abstract: Increased expression of Pituitary Tumor Transforming Gene 1 (Pttg1) has been shown in various tumor cells, including breast cancer (BC). However, the precise role of Pttg1 in the tumorigenesis is not clarified yet. Here, we examined BC from the patients and detected significant increases and correlation in Pttg1 and phosphorylated SMAD3 (pSMAD3), a key effector of activated transforming growth factor β (TGFβ) receptor signaling pathway. Pttg1 levels were then modulated by transgene or small hairpin RNA (shRNA) in a human BC cell line, BT474, respectively. We found that Pttg1 overexpression increased the proliferation of BC cells in vitro and in vivo, while Pttg1 inhibition decreased proliferation of BC cells in vitro and in vivo. Moreover, phosphorylation of SMAD3 by TGFβ1 was significantly inhibited by Pttg1 overexpression, suggesting that Pttg1 may promote growth of BC cells by inhibiting pSMAD3-mediated cell-growth inhibition. Thus, Pttg1 appears to be a novel therapeutic target for controlling the tumorigenesis of BC.
authors.affiliation: Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, 200065, Shanghai, China, zhangtjsh@126.com.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Qicheng
authors.initials: Q
authors.lastname: Zhao
authors.forename: Songlin
authors.initials: S
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Lin
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D064249:Securin / Q000502:physiology*; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C497790:SMAD3 protein, human; D064249:Securin; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; C578002:pituitary tumor-transforming protein 1, human