PCNA (Proliferating Cell Nuclear Antigen) Antibody Review

Introduction

also called cyclin, is a 36-KD auxiliary protein of DNA polymerase-delta, that has been found to be a useful marker in immunocytochemical studies of cell proliferation because its expression correlates with the proliferative state of the cell. PMID: 8986050
a nuclear protein involved in DNA-synthesis and repair. PMID: 14642618
associated with S phase and DNA replication of the cell cycle. PMID: 15890234
an essential protein for both DNA replication and DNA repair. PMID: 15806324
a key component of the DNA replication machinery involved in the process of DNA elongation, recombination, methylation and repair. PMID: 15584900
a DNA polymerase delta accessory protein, and is an indicator of the proliferative state of the cell. PMID: 12924172
a eukaryotic DNA replication factor, functions not only as a processivity factor for DNA polymerase delta but also as a binding partner for multiple other factors. PMID: 12171929
an auxiliary protein of the DNA polymerase delta, belonging to the cyclin family, which attains appreciable levels only in those phases of the cell cycle in which DNA synthesis occurs. PMID: 10841451, PMID: 9042536

Normal Expression

cell proliferation markers p120, Ki-67 and proliferating cell nuclear antigen (PCNA) recognize nuclear antigens. PMID: 14748788
The patterns of PCNA positivity showed normal proliferation in the telencephalon of the adult male Serinus serinus. This activity was shown by cells interposed among the epithelial cells lining the lateral side of each ventricular cavity, both in correspondence to the apical tracts and declivities of the ependyma and arranged, here and there, either in groups or slightly separated. PMID: 16038380
In morphologically normal esophageal epithelium, esophagin stains the granular layer cells, principally in their cell membrane portions. PCNA, in contrast, stains the nuclei of cells in the parabasal and basal layers. PMID: 15221970
A distinct reduction in the percentage of PCNA-positive nuclei was detected starting at day 19 of the prenatal period, and these cells were rarely observed on postnatal days 30 and 60. PMID: 12389741
During kidney development, proliferating cell nuclear antigen (PCNA) is expressed in the nephrogenic zone and is downregulated rapidly as renal epithelial cells enter terminal differentiation and acquire functional characteristics. PMID: 12217864
In neonatal testes, some PCNA-positive spermatogonia, Sertoli cells, peritubular cells, and Leydig cells were detected. In early infantile testes, only a few of these cell types were positive. In late infantile testes, the numbers of positive cells were greater than in the earlier developmental stages. In pubertal testes, the numbers of positive spermatogonia, spermatocytes, Sertoli cells, peritubular cells, and Leydig cells were considerably higher. In adult testes, a larger percentage of spermatogonia and spermatocytes was positive, and peritubular cells and Leydig cells were occasionally positive; secondary spermatocytes, spermatids, and Sertoli cells were not positive. PMID: 11491403
Positive staining for this protein was seen as granular pattern in the nucleus and in the cytoplasm. In the nucleus the gold particles were seen to be associated with heterochromatin and euchromatin of the leukemia cells. In cytoplasm it was found on the endoplasmic reticulum and associated with ribosomes. PMID: 11130245
Immunohistochemistry was also performed using 19F4 and PC10, and staining of progenitor cell nuclei in the subventricular zone was observed with both antibodies. Whereas 19F4 immunostaining was restricted to progenitor cells, PC10 immunostaining was also found in postmitotic nonproliferating cell nuclei. PMID: 10891596
Using an immunocytochemical method that exploits this proliferative marker, we observed a certain PCNA positivity in the telencephalon of normal adult individuals of Triturus carnifex. PMID: 10841451
PCNA was expressed in 20% of normal kidneys and in 38% of renal biopsies with GN. PMID: 9225147
co-localization of p21 and PCNA in the nucleus of normal and repair-deficient human cells indicates that p21 and PCNA interact during post-damage events. PMID: 8673466

Abnormal Expression

There were abundant levels of survivin and PCNA immunoreactivity in the nucleus and/or cytoplasm of the osteosarcoma cells. All cells essentially revealed the cytoplasmic localization and the nuclear signals of survivin in same cases, while PCNA from the majority of cases predominantly showed nuclear expression. PMID: 16705726
PCNA was expressed in hematopoietic progenitor cells but not in mature neutrophils, eosinophils or erythroid cells. Some PCNA+ cells are scattered in the hematopoietic compartment of the kidney while others are closely associated with renal tubular cells. PCNA was also expressed in spermatogonial stem cells and intestine crypts, consistent with its role in cell proliferation and DNA synthesis. In embryos, PCNA is expressed in the brain, spinal cord and intermediate cell mass (ICM) at 24 h-post fertilization. PMID: 16028068
Brains of 50 cats of different age and gender, dying of various diseases, were examined. Strong PCNA clone PC10 expression could be observed in neurones of the cerebellar cortex and the vestibular nuclei, whereas entorhinal cortex, lateral geniculate nucleus and cerebral cortex revealed only weak immunolabelling. The PCNA clone 19F4 labelled numerous neurones in vestibular nuclei and some Purkinje cells of the cerebellum. PMID: 15610484
highest PCNA and Ki-67 LI values were detected in medulloblastoma, malignant meningioma, primitive neuroectodermal tumor (PNET) and glioblastoma (GBM) groups, while pilocytic astrocytoma, meningioma, craniopharyngioma and oligodendroglioma showed the lowest va both p53 expression and PCNA are markers of poor differentiation in breast cancer. PMID: 10927863
PCNA was predominantly found in heterochromatin of the nucleus of laryngeal carcinoma cells in a granular pattern. Positivity for PCNA was not found in nucleoli. In 4 cases, positive staining was observed both in nucleus and cytoplasm. In the cytoplasm, it was found to be present on the endoplasmic reticulum and on ribosomes throughout the cytoplasm. PMID: 10824607
density of PCNA-positive cells was higher in Jimpy than in normal spinal cords, and about 50% of PCNA-positive cells in the Jimpy white matter were identified as cells from the oligodendrocyte line, 30% were microglial cells and 20% were astrocytes. PMID: 9042536
suprabasal PCNA expression could be a marker of dysplasia in oral mucosa, indicating a special proliferative cellular state in those lesions. PMID: 8986050

Expression Alteration

expression level of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, in the liver was significantly enhanced in the deficient rats, suggesting that cell proliferation is abnormally activated in the liver under Cbl-deficient conditions. PMID: 16967760
The percentage of PCNA-positive hepatocytes was significantly higher in the group given diet containing aflatoxin B(1) than in the other groups. PMID: 16269167
PCNA immunoreactivity was undetectable in the normal retina, but was specifically induced in neurons of the inner retina within 1 h after reperfusion and was sustained for at least 4 weeks. PMID: 10744062

Function

PCNA Activates the Holliday Junction Endonuclease Hjc. PMID: 17011573
MIB-1/PCNA proliferative markers can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smear. PMID: 15945082
proved to be an independent prognostic indicator in predicting disease-free and overall survival in breast carcinoma patients. PMID: 15857596
an independent predictor of progression, especially in patients with a low risk of progression according to predefined criteria. PMID: 15705097
PCNA and AgNOR expressions correlate with proliferative activity, growth rate and histological malignancy, reaching high values in highly malignant and early recurrent tumors. PMID: 15654669
expression of Ki-67, PCNA proteins were closely connected with the high grade of tumour malignancy. PMID: 15638377
GFP-PCNA is a accurate and non-toxic marker of S-phase in embryos during early development. PMID: 15584900
Ki-67 and PCNA expression is suggested as a marker of stromal element proliferation. PMID: 15039920
Ki67 and PCNA immunostaining in paraffin sections may be useful for the prediction of survival in patients with anorectal malignant melanoma. PMID: 12460204
Measuring cell proliferation in the rectal mucosa. comparing bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) assays. PMID: 10942872
PCNA index can be used in decision making for treatment and assessment of prognosis in laryngeal carcinomas. PMID: 9865753
a prognostic marker for renal cell carcinoma (RCC). PMID: 9584051
PCNA could be used as a marker in predicting the clinical outcome in supraglottic cancers. PMID: 9350310

Applications

Electron Microscopy (EM)

PCNA antigen was localized at the light and electron microscopes level in two human leukemia cell lines HL-60 and K-562. PMID: 11130245
Immunoelectron microscopy of PCNA as an efficient marker for studying replication times and sites during pollen development. PMID: 11072795
Streptavidin-gold was used for the immunolocalization of PCNA and Ki-67 antigen at the ultrastructural level with a postembedding technique in biopsies of 15 patients with laryngeal squamous cell carcinoma. PMID: 10824607
Ultrastructural immunolocalization of cyclin/PCNA in synchronized 3T3 cells. PMID: 2571512

Flow Cytometry (FC)

Flow cytometry expression of p53 and PCNA in oral/oropharynx carcinomas and their lymph node metastases. PMID: 14666613
a flow cytometric method for detection of PCNA in solid head and neck tumors and how these data correlate with outcome. PMID: 9128950
Comparative flow cytometric analysis of DNA-bound PCNA and DNA content as estimators of S-phase cells in cell cultures. PMID: 8844110
Comparison of proliferating cell nuclear antigen (PCNA) staining and BrdUrd-labelling index under different proliferative conditions in vitro by flow cytometry. PMID: 7893842
Comparative flow cytometric analysis of Ki-67 and proliferating cell nuclear antigen (PCNA) in solid neoplasms. PMID: 7851161
Identification of S-phase cells with PC10 antibody to proliferating cell nuclear antigen (PCNA) by flow cytometric analysis. PMID: 7913107
Flow cytometric measurement of proliferating cell nuclear antigen (PCNA) in solid tumors. PMID: 8165522
Comparative flow cytometric analysis of proliferating cell nuclear antigen (PCNA) antibodies in human solid neoplasms. PMID: 7909288
Flow cytometric analysis of the expression of PCNA during the cell cycle in HeLa cells and effects of the inhibition of DNA synthesis on it. PMID: 7904555
Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer. PMID: 1356517

Immunohistochemistry (IHC)

By means proliferating cell nuclear antigen (PCNA) immunohistochemistry, we have provided a detailed neuroanatomical mapping of proliferative activity during development and adulthood in the frog (Rana esculenta) brain. PMID: 16987635
Sections from paraffin embedded tissues were retrieved and stained with antibodies against PCNA for proliferation and CD34 for angiogenesis using immunohistochemical technique. PMID: 16868689
Immunohistochemical localization of cytokeratin 19, involucrin and proliferating cell nuclear antigen (PCNA) were examined in human cultured gingival epithelial sheets samples from twenty patients. PMID: 16459887
The expression pattern of S6K1/2, Ki-67 and PCNA has been investigated by immunohistochemical analysis of formalin fixed paraffin embedded sections of 40 human breast adenocarcinomas. PMID: 15995633
In paraffin sections of 60 ductal breast cancers, immunocytochemical reactions were performed to detect expression of Ki67 and PCNA. PMID: 15844560
objective of this study was to create and evaluate a routine (macro) using Image-Pro Plus 4.5 software (Media Cybernetics, Silver Spring, USA) for automatic counting of labeled nuclei by proliferating cell nuclear antigen (PCNA) immunohistochemistry. PMID: 15311310
expression of proliferating cell nuclear antigen (PCNA) was studied in plasma cells in bone marrow biopsies from patients with multiple myeloma (MM) using a double immunostaining method. PMID: 15000866
Two different immunohistochemical markers were used to analyze cell proliferation: (1) injection of the thymidine analogue BrdU and subsequent immunohistochemical staining for BrdU-positive nuclei, and (2) the antibody against the "proliferating cell nuclear antigen" (PCNA). In comparison, both methods revealed similar results concerning the types of proliferating cells at the different time points and the two groups. Labeling indices of both methods showed very good correlation. PMID: 12632384
p53 And PCNA expression was analyzed by immunohistochemistry and evaluated quantitatively by image analysis. PMID: 12630078
aim of our study was the immunohistochemical evaluation of Ki-67 and proliferating cell nuclear antigen (PCNA) expression in prostate cancer (PCa) following radical prostatectomy and analysis of its relationship to chosen anatomo-clinical and morfological parameters of the tumours. PMID: 12533969
In this study, immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and Ki-67 was determined in 10 cases of parathyroid carcinomas. PMID: 10819371
Paraffin sections of 51 breast carcinomas were stained with primary antibody to PCNA. Nuclear PCNA expression in 100 randomly selected tumor cells from marked areas was manually graded from 0 to 3. Antigen expression was also calculated by a cell analysis system. PMID: 10696455
Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) was performed in skin from patients with various malignant and nonmalignant skin diseases using anti-PCNA monoclonal antibodies. PMID: 10482011
How should PCNA be assessed? Total of stained cells or only the most intensely stained ones? it is more appropriate considering all the stained cells as representative of PCNA indices, thus reflecting tumor aggressiveness. PMID: 9778886
immunohistochemical status of the PCNA and p53 proteins were determined on paraffin-embedded sections from 128 patients with TCC of the urinary bladder, using PC-10 and DO7 as the primary antibodies. PMID: 9179692
A streptavidin-biotin immunoperoxidase method (ABC) using a monoclonal antibody PC10 demonstrated nuclear staining with varying intensity and distribution in all tumor specimens. PMID: 8917372
A comparison of proliferation markers (BrdUrd, Ki-67, PCNA) determined at each cell position in the crypts of normal human colonic mucosa. PMID: 8839702
The proliferation rate in livers of 120 mice (60 males and 60 females) was analyzed by immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression on ethanol-fixed/paraffin-embedded specimens. A good correlation between the degree of BrdU and PCNA labeling was observed and, as expected, the percentage of PCNA expressing cells was generally higher than the percentage of BrdU-positive cells. PMID: 7987078

Western Blot (WB)

DNA-bound and detergent-soluble fractions of PCNA and p21 were analyzed by immunoblotting. PMID: 14642618
two monoclonal antibodies against PCNA, PC10 and 19F4, were used for Western blot analysis. Monoclonal antibody PC10, but not 19F4, detected a band in the adult mouse brain extract. This PC10-reactive protein in the brain displayed a more acidic isoelectric point than PCNA by two-dimensional gel electrophoresis. PMID: 10891596