Abstract
Purpose
p12CDK2-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 p12CDK2-AP1 in breast cancer progression.
Methods
Expression of p12CDK2-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.
Results
p12CDK2-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 p12CDK2-AP1 over-expression lentivirus, but enhanced in cells that transduced with p12CDK2-AP1 RNAi lentivirus. p12CDK2-AP1 over-expression led to G0/G1 phase arrest in the cell cycle and caused expression changes of cell cycle-related genes (CDK2, CDK4, p16Ink4A, p21Cip1/Waf1). Furthermore, p12CDK2-AP1 over-expression inhibited in vivo tumor growth in immunodeficiency mice, supporting an inhibitory role for p12CDK2-AP1 in breast cancer development.
Conclusions
As a cell cycle regulator, p12CDK2-AP1 is involved in the development of breast cancer and maybe a potential therapeutic candidate to suppress tumorigenicity in breast cancer.
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Zhou, W., Guan, X., Wang, L. et al. p12CDK2-AP1 inhibits breast cancer cell proliferation and in vivo tumor growth. J Cancer Res Clin Oncol 138, 2085–2093 (2012). https://doi.org/10.1007/s00432-012-1286-z
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DOI: https://doi.org/10.1007/s00432-012-1286-z