p27Kip1 is inactivated in human colorectal cancer by cytoplasmic localization associated with activation of Akt/PKB

  • Authors:
    • C. Bottini
    • F. Platini
    • M. Rinaldi
    • M. Leutner
    • O. Alabiso
    • M. Garavoglia
    • L. Tessitore
  • View Affiliations

  • Published online on: January 1, 2009     https://doi.org/10.3892/ijo_00000130
  • Pages: 69-77
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Abstract

p27Kip1 is a nuclear member of the Kip/Cip family of cyclin-dependent kinase inhibitors and is a negative cell cycle regulator that is thought to play a role in tumour suppression. Reduced levels of p27Kip1 are frequent in human cancers and these have been associated with poor prognosis. We have analysed p27Kip1 expression and intracellular localization in 70 human colorectal cancers by western blotting and immunohistochemistry and the results related to Akt expression and clinical pathological parameters. p27Kip1 protein expression, as evaluated by western blotting, was absent or reduced in about 63% of colorectal cancers compared with both peritumoral and normal tissue. Cytoplasmic p27Kip1 was detected, by immunohistochemical analysis, in 30% (21 of 70) of cases indicating that translocation of p27Kip1 protein into the cytoplasm may be responsible for p27Kip1 inactivation. The analysis of phosphorylated Akt by western blotting indicated that it was expressed in 38% (8 of 21) of tumours showing cytoplasmic p27Kip1. Patients whose cancer presented accumulation of cytoplasmic p27Kip1 showed poorer outcomes for cancer-related relapse and survival. These results suggest that cytoplasmic p27Kip1 localization, associated or not with Akt activation, may contribute to colorectal tumorigenesis and metastasis and it may be useful as a negative prognostic factor for the outcome of patients with colorectal cancer.

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January 2009
Volume 34 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Bottini C, Platini F, Rinaldi M, Leutner M, Alabiso O, Garavoglia M and Tessitore L: p27Kip1 is inactivated in human colorectal cancer by cytoplasmic localization associated with activation of Akt/PKB. Int J Oncol 34: 69-77, 2009
APA
Bottini, C., Platini, F., Rinaldi, M., Leutner, M., Alabiso, O., Garavoglia, M., & Tessitore, L. (2009). p27Kip1 is inactivated in human colorectal cancer by cytoplasmic localization associated with activation of Akt/PKB. International Journal of Oncology, 34, 69-77. https://doi.org/10.3892/ijo_00000130
MLA
Bottini, C., Platini, F., Rinaldi, M., Leutner, M., Alabiso, O., Garavoglia, M., Tessitore, L."p27Kip1 is inactivated in human colorectal cancer by cytoplasmic localization associated with activation of Akt/PKB". International Journal of Oncology 34.1 (2009): 69-77.
Chicago
Bottini, C., Platini, F., Rinaldi, M., Leutner, M., Alabiso, O., Garavoglia, M., Tessitore, L."p27Kip1 is inactivated in human colorectal cancer by cytoplasmic localization associated with activation of Akt/PKB". International Journal of Oncology 34, no. 1 (2009): 69-77. https://doi.org/10.3892/ijo_00000130