p12(CDK2-AP1) inhibits breast cancer cell proliferation and in vivo tumor growth

J Cancer Res Clin Oncol. 2012 Dec;138(12):2085-93. doi: 10.1007/s00432-012-1286-z. Epub 2012 Jul 25.


Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Cycle / genetics
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Disease Progression
  • Down-Regulation
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation


  • CDK2AP1 protein, human
  • Tumor Suppressor Proteins