P27kip1

Sources/Clones
Lab Vision Corp (DCS70), Pharmingen (G173-524) and Transduction Laboratory.

Fixation/Preparation
The anti-p27 antibody is immunoreactive in fixed paraffin-embedded sections but only following HIER in citrate buffer at neutral pH.

Background
The p27kip1 (p27) gene encodes an inhibitor of cyclin-dependent kinase (CDK) activity. Two families of proteins that generally inhibit cell cycle progression regulate the activity of cyclin-dependent kinase complexes. These are the INK4 group of p16, p15, p18 and p19, which may have suppressor functions and whose activities are dependent on a normal retinoblastoma protein and show maximal expression during S-phase, and the group of CDK inhibitors which include p21/WAF1/CIP1, p27kip1 and p57/kip2. Overexpression of the latter group inhibits kinase activities of several cyclins and causes cell cycle arrest. The role of kip protein in regulating cell cycle progression in normal and neoplastic cells has not been elucidated although p27-deficient mice develop multiple organ hyperplasia, suggesting that this CDK inhibitor has anti-proliferative activity in vivo (Toyoshima & Hunter, 1994; Hengst & Reed, 1996).

Applications
Several studies have revealed a marked decrease in the percentage of cells expressing p27 in benign and malignant neoplasms compared to normal tissues, with an inverse relationship to Ki-67 antigen, a marker of cell proliferation. Studies with transgenic knockout mice deficient in p27 have shown that p27 protein inhibits proliferation in tissues such as the thymus, pituitary and spleen, leading to hyperplasias of these organs. The exact role of p27 abnormalities in tumor development remains uncertain. Mutations are relatively uncommon in the p27 gene and other mechanisms such as translational control with decreased p27 or downregulation of p27 by specific mitogens may occur during tumor development. The observations that p27 levels are markedly decreased in highly malignant tumors such as anaplastic thyroid carcinomas compared with normal thyroid and benign adenomas suggests that loss of p27 expression may be associated with tumor progression. Evaluation of p27 protein has the potential of predicting the biological behavior of various neoplasms and can be employed to study cell cycle regulation during tumor progression.

Comments
The antibody from Transduction Laboratory, Lexington, KY, is immunoreactive in routine-fixed, paraffin-embedded tissues (Lloyd et al, 1997). The antigen is located in the nucleus. Current applications are primarily in research.

References
•Hengst L, Reed SI 1996. Translational control of p27kip1 accumulation during the cell cycle. Science 271: 1861-1864. Lloyd RV, Jin L, Qian X, Kulig E 1997 Aberrant p27kip1 expression in endocrine and other tumors. American Journal of Pathology 150: 401-407.

•Toyoshima H, Hunter T 1994 p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 78: 67-74.

Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.