title: DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway.
abstract: Breast cancer is one of the most common malignant neoplasms diagnosed in females worldwide. Bone morphogenetic proteins (BMPs), which belong to the TGF-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration and apoptosis in breast cancer. BMPs can bind to type I and II serine/threonine kinase receptors to regulate cell proliferation, invasion, migration, and apoptosis. Type I receptors are expressed in various breast cancer cell lines and primary tumor samples. Activin‑like kinase 2 (ALK2) is generally expressed in breast cancer cells (MDA-MB-231, MCF7, SK-BR-3 and MDA-MB‑468); however, the effect of ALK2 on the proliferation and metastasis of breast cancer cells remains unknown. We used a dominant-negative mutant of ALK2 to research the function of ALK2. We aimed to ascertain whether dominant-negative mutant ALK2 adenovirus vector (DNALK2) receptors can compete with wild-type ALK2 receptors. The present study showed that DNALK2 inhibited the growth, migration and metastasis of breast cancer cells by inhibiting the SMAD-dependent pathway and downregulating connective tissue growth factor and inhibitor of differentiation 1 expression, in vivo and in vitro. These observations indicate that ALK2 is a potential therapeutic agent for the treatment of breast cancer.
authors.affiliation: Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hong Lei
authors.initials: HL
authors.lastname: Feng
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Fei
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D051785:Smad Proteins; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I