Wang Ke, Sun Xiaoxiao, Feng Hong Lei, Fei Chang, Zhang Yan
Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China.
Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
Oncol Rep. 2017 Feb;37(2):879-886. doi: 10.3892/or.2016.5343. Epub 2016 Dec 30.
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.
乳腺癌是全球范围内女性中最常见的恶性肿瘤之一。骨形态发生蛋白（BMPs）属于转化生长因子-β超家族，可调节多种细胞反应，包括乳腺癌中的细胞增殖、分化、黏附、迁移和凋亡。BMPs可与I型和II型丝氨酸/苏氨酸激酶受体结合，以调节细胞增殖、侵袭、迁移和凋亡。I型受体在各种乳腺癌细胞系和原发性肿瘤样本中均有表达。激活素样激酶2（ALK2）通常在乳腺癌细胞（MDA-MB-231、MCF7、SK-BR-3和MDA-MB-468）中表达；然而，ALK2对乳腺癌细胞增殖和转移的影响尚不清楚。我们使用ALK2的显性负性突变体来研究ALK2的功能。我们旨在确定显性负性突变体ALK2腺病毒载体（DNALK2）受体是否能与野生型ALK2受体竞争。本研究表明，DNALK2在体内和体外通过抑制SMAD依赖途径并下调结缔组织生长因子和分化抑制因子1的表达，抑制乳腺癌细胞的生长、迁移和转移。这些观察结果表明，ALK2是治疗乳腺癌的一种潜在治疗剂。
