Proliferating cell nuclear antigen PCNA

Nuclear-specific proteins, such as Ki-67 (MIB-1), proliferating cell nuclear antigen (PCNA) and protein 53 have an essential role in cell proliferation and are widely accepted proliferation marker. They are present in all dividing cells of normal and tumor tissues, but absent in resting cells. 

Immunohistochemical Detection of Cells in the Division Cycle Using Antibodies to Proliferating Cell Nuclear Antigen (PCNA)... 

Many proliferation-associated antigens have been reported as clinically useful indicators of proliferative activity (1). Of these, the so-called proliferating cell nuclear antigen (PCNA) and Ki-67 have been identified as the most useful in both immunohistochemistry (see Chapter 27) and flow cytometry (FCM). PCNA is an auxiliary protein to DNA polymerase 8 (2,3) and is intimately associated with DNA replication, but also DNA repair (4,5). Ki-67 is a large protein associated with nuclear nonhistone proteins (6,7), and is expressed in all actively proliferating cells (8,9). Expression of these two proteins, in a cell population should equate to the growth fraction, i.e., the proportion of cells involved in an active cell cycle. However, there are apparent inconsistencies when these two proteins have been compared with one another (10) and with other methods of assessing cell proliferation (11). 

Steck, K. and El-Naggar, A K (1994) Comparative flow cytometric analysis of Ki-67 and proliferating cell nuclear antigen (PCNA) in solid neoplasms Cytometry 17,258—265... 

Landberg, G and Roos, G. (1991) Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 antigen m human malignant hematopoietic cells. Acta Oncol 30,917-921... 

Funato, H., Yoshimura, M., Ito, Y., Okeda, R., and Ihara, Y. 1996. Proliferating cell nuclear antigen (PCNA) expressed in human leptomeninges. J. Histochem. Cytochem. 44 1261-1265. 

Griffey, S. M., Kraegel, S. A., and Madewell, B. R., 1999. Proliferation indices in spontaneous canine lung cancer proliferating cell nuclear antigen (PCNA), Ki-67 (M1B1) and mitotic counts. 7. Comp. Pathol. 720 321-332. 

Haerslev, T., and Jacobsen, G. K. 1994. Microwave processing for immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded tissue. APMIS 102 395-100. 

Mintze, K., Macon, N., Gould, K. E., and Sandusky, G. E., 1995. Optimization of proliferating cell nuclear antigen (PCNA). Immunohistochemical staining A comparison of methods using three commercial antibodies, various fixation times, and antigen retrieval solutions. J. Histotechnol. 78 25-30. 

Munoz de Toro de Luque, M., and Luque, E. H. 1995. Effect of microwave pretreatment on proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections. J. Histotechnol. 78 11-16. 

Wrobel, K.-H., Bickel, D., and Kujat, R. 1996. Immunohistochemical study of seminiferous epithelium in adult bovine testes using monoclonal antibodies against Ki-67 protein and proliferating cell nuclear antigen (PCNA). Cell Tissue Res. 283 191-201. 

FEN-l s endonuclease activity removes flap substrates by a unique mechanism. As illustrated in Figure 7.2, FEN-1 is first loaded onto the 5 end of flaps (Tom et al., 2000 Wu et al., 1996). It then slides down the flap strand and cleaves the flap at the point of annealing (Tom et al., 2000 Wu et al., 1996). Proliferating cell nuclear antigen (PCNA), a homotrimeric protein primarily found as a cofactor promoting the activity of DNA polymerase 6(Eissenberg et al., 1997), can promote FEN-l s endonuclease activity five- to 50-fold (Eisscnberg et al, 1997 Wu et al., 1996). 

Figure 2.39 A DNA clamp protein - a trimer of the protein Proliferating Cell Nuclear Antigen (PCNA). The three different trimer units are shown in different colours (image courtesy of www. wikipedia.org). 

Figure 6. Staining obtained with two antibody clones to proliferating cell nuclear antigen (PCNA). Antigen retrieval and staining procedures were identical for the two antibodies, (a) Clone 19A2 showed a proliferating index of 75% compared to (b) to a 98% proliferating index in the adjacent section of breast cancer when stained with clone PC 10.

Leong AS-Y, Milios J, Tang SK. Is immunolocalisation of proliferating cell nuclear antigen (PCNA) in paraffin sections a valid index of cell proliferation Appl. Immunohistochem. 1993 1 127-3 5. 

---