Department of Oncology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, China.
J Cancer Res Clin Oncol. 2012 Dec;138(12):2085-93. doi: 10.1007/s00432-012-1286-z. Epub 2012 Jul 25.
p12(CDK2-AP1) is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities and shows to interfere in DNA replication. Here, we aim to elucidate the role of p12(CDK2-AP1) in breast cancer progression.
Expression of p12(CDK2-AP1) protein was examined in 60 pairs of breast cancer specimens and adjacent non-tumor tissues using immunohistochemistry assay. Loss-of-function and gain-of-function analysis was performed on MCF-7 and MDA-MB-231 breast cancer cells. Routine assays including MTT, colony formation, flow cytometry, and tumorigenesis in nude mice were performed and cell cycle regulators were analyzed.
p12(CDK2-AP1) was found to be significantly downregulated in 60 breast cancer tissues compared to corresponding non-tumorous tissues. The proliferation and colony formation ability was inhibited in cells that transduced with p12(CDK2-AP1) over-expression lentivirus, but enhanced in cells that transduced with p12(CDK2-AP1) RNAi lentivirus. p12(CDK2-AP1) over-expression led to G0/G1 phase arrest in the cell cycle and caused expression changes of cell cycle-related genes (CDK2, CDK4, p16(Ink4A), p21(Cip1/Waf1)). Furthermore, p12(CDK2-AP1) over-expression inhibited in vivo tumor growth in immunodeficiency mice, supporting an inhibitory role for p12(CDK2-AP1) in breast cancer development.
As a cell cycle regulator, p12(CDK2-AP1) is involved in the development of breast cancer and maybe a potential therapeutic candidate to suppress tumorigenicity in breast cancer.
p12（CDK2-AP1）是一种生长抑制因子，可负调控细胞周期蛋白依赖性激酶 2（CDK2）的活性，并干扰 DNA 复制。本研究旨在阐明 p12（CDK2-AP1）在乳腺癌进展中的作用。
采用免疫组织化学法检测 60 对乳腺癌组织及其相应非肿瘤组织中 p12（CDK2-AP1）蛋白的表达。在 MCF-7 和 MDA-MB-231 乳腺癌细胞中进行了 p12（CDK2-AP1）的功能丧失和功能获得分析。进行了常规的 MTT、集落形成、流式细胞术和裸鼠成瘤实验，并分析了细胞周期调控因子。
与相应的非肿瘤组织相比，p12（CDK2-AP1）在 60 例乳腺癌组织中明显下调。转染 p12（CDK2-AP1）过表达慢病毒的细胞增殖和集落形成能力受到抑制，而转染 p12（CDK2-AP1）RNAi 慢病毒的细胞增殖和集落形成能力增强。p12（CDK2-AP1）过表达导致细胞周期 G0/G1 期阻滞，并引起细胞周期相关基因（CDK2、CDK4、p16（Ink4A）、p21（Cip1/Waf1））的表达变化。此外，p12（CDK2-AP1）过表达抑制了免疫缺陷小鼠体内的肿瘤生长，表明 p12（CDK2-AP1）在乳腺癌的发生发展中起抑制作用。
作为细胞周期调控因子，p12（CDK2-AP1）参与了乳腺癌的发生发展，可能是抑制乳腺癌致瘤性的潜在治疗靶点。
