• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.756-765
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• 1997

Background : To study the prognosis of patients with lung cancer, many investigators have reported the methods to detect cell proliferation in tissues including PCNA, thymidine autoradiography, flow cytometry and Ki-67. PCNA, also known as cyclin, is a cell related nuclear protein with 36KD intranuclear polypeptide that is maximally elevated in S phase of proliferating cells. In this study, PCNA was identified by paraffin-embedding tissue using immunohistochemistry which has an advantage of simplicity and maintenance of tissue architecture. The variation of PCNA expression is known to be related with proliferating fraction, histologic type, anatomic(TNM) stage, degree of cell differentiation, S-phase fraction and survival rate. We analyzed the correlation between PCNA expression and S-phase fraction, survival. Method : To investigate expression of PCNA in primary lung cancer, we used immunohistochemical stain to paraffin-embedded sections of 57 resected primary non-small cell lung cancer specimen and the results were analyzed according to the cell type, cell differentiation, TNM stage, S-phase fraction and survival. Results : PCNA expression was divided into five group according to degree of staging(-, +, ++, +++, ++++). Squamous cell type showed high positivity than in adenocarcinoma. Nonsignificant difference related to TNM stage was noticed. Nonsignificant difference related to degree of cell differentiation was noticed. S-phase fraction was increased with advance of PCNA positivity, but it could not reach the statistic significance. The 2 year survival rate and median survival time were -50% 13 months, +75% 41.3 months, ++73% 33.6 months, +++67% 29.0 months, ++++25% 9 months with statistic significance (P<0.05, Kaplan-Meier, generalized Wilcox). Conclusion : From this study, PCNA expression was high positive in squamous cell cancer. And, there was no relationship between PCNA positivity and TNM stage, cellular differentiation or S-phase fraction. But, the patients with high positive PCNA staining showed poor survival rate than the patients with lower positive PCNA staining (p<0.05). It was concluded that PCNA immunostaining is a simple and useful method for survival prediction in paraffin embedded tissue of non-small cell lung cancer.

• Journal of Microbiology and Biotechnology
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• v.26 no.4
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• pp.637-647
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• 2016

Proliferating cell nuclear antigen (PCNA) is a critical eukaryotic replication accessory factor that supports DNA binding in DNA processing, such as DNA replication, repair, and recombination. PCNA consists of three toroidal-shaped monomers that encircle double-stranded DNA. The diverse functions of PCNA may be regulated by its interactions with partner proteins. Many of the PCNA partner proteins generally have a conserved PCNA-interacting peptide (PIP) motif, located at the N- or C- terminal region. The PIP motif forms a 3₁₀ helix that enters into the hydrophobic groove produced by an interdomain-connecting loop, a central loop, and a C-terminal tail in the PCNA. Post-translational modification of PCNA also plays a critical role in regulation of its function and binding partner proteins. Structural and biochemical studies of PCNA-protein will be useful in designing therapeutic agents, as well as estimating the outcome of anticancer drug development. This review summarizes the characterization of eukaryotic PCNA in relation to the protein structures, functions, and modifications, and interaction with proteins.

• Journal of Yeungnam Medical Science
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• v.12 no.1
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• pp.1-9
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• 1995

A monoclonal antibody to PCNA, which can be used on routinely processed tissue, was applied to 25 cases of gastric adenomas and 64 cases of gastric adenocarcinomas in order to diffentiate adenoma and adenocarcinoma and also to evaluate the prognostic value in adenocarcinoma. The results were summerized as follows: The peNA labelling index was $29.14{\pm}12.77%$ in control, $44.09{\pm}17.11%$ in adenoma and $80.15{\pm}10.69$ in adenocarcinoma, resulting in significant increase in adenocarcinoma compared to adenoma. In adenocarcinoma, no significant correlation was observed between PCNA labelling index and histologic grade, and there was increased tendency of PCNA labelling index in proportion to depth of invasion without statistical significance. The PCNA index was significantly increased in advanced adenocarcinoma compared to early gastric carcinoma, and also in positive nodal metastasis group than in negative group. From above results, the PCNA stain will be able to provide a helpful method for the differential diagnosis between gastric adenoma and adenocarcinoma, and could be a useful prognostic factor in adenocarcinoma if other factors are considered together.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.2
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• pp.142-149
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• 2001

To investigate the correlation between the clinical features and the expression of p53, PCNA, and Ki-67 of the head neck squamous cell carcinoma, immunohistochemicalstaining of p53, PCNA, and Ki-67 on the paraffin embedded tissue blocks of 116 surgically removed specimens were done. The staining intensity was divided as grade 1 to grade 3 and the results were statistically analysed. 1. The positive reation rates of cell proliferation markers (PCNA and Ki-67) were higher than that of p53. There was significant correlations of the PCNA and Ki-67 expression but there was no significant correlations between p53 and PCNA or p53 and Ki-67. 2. There were no significant correlation between the expression of p53, PCNA and Ki-67 and tumor site or tumor size. 3. There was no significant differences in the positive response according to the nodal status. The node metastasis groups revealed that higher proportion of grade 3 staining of PCNA and Ki-67 than node negative group. From the above results it is concluded that p53 and cell proliferation markers PCNA and Ki-67 might have their unique mechanism involving in the growing and progression of tumor. Overexpression of p53 does not appear to represent an independent prognostic marker in head neck squamous cell carcinoma.

• Journal of Korean Physical Therapy Science
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• v.10 no.1
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• pp.198-205
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• 2003

We evaluated the effect of low power GaAsAl laser on re-epithelization in full-thickness excisional wound of rat skin. Two full-thickness excisions were made on the back of the experimental animals. Low power laser applications with 10mW intensity were treated experimental animals twice a day for 7 days. On the seventh postoperative day the quantitative analysis of re-epithelization was performed using immunohistochemical staining for proliferating cell nuclear antigen (PCNA). The majority of PCNA immunoreactive cells was observed at epithelial cells in the margin of full thickness excisional wound. The low power laser treatments significantly increased the number of PCNA immunoreactive cell as compared to that of non treated animal group (p<0.01). The shape of PCNA immunoreactive cell appeared as small dark, round to ovoid structures. Most PCNA immunoreactive cells exhibited a high intensity of staining that contrasted sharply with the surrounding background. In conclusion, these findings suggest that GaAlAs laser treatments effectively enhance the epithelial wound healing by the stimulating cell proliferation. Furthermore, the majority of cell proliferation occurred in the margin of full thickness excisional wound.

• Molecules and Cells
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• v.26 no.1
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• pp.5-11
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• 2008

Stalled DNA replication forks activate specific DNA repair mechanism called post-replication repair (PRR) pathways that simply bypass DNA damage. The bypassing of DNA damage by PRR prevents prolonged stalling of DNA replication that could result in double strand breaks (DSBs). Proliferating cell nuclear antigen (PCNA) functions to initiate and choose different bypassing pathways of PRR. In yeast, DNA replication forks stalled by DNA damage induces monoubiquitination of PCNA at K164, which is catalyzed by Rad6/Rad18 complex. PCNA monoubiquitination triggers the replacement of replicative polymerase with special translesion synthesis (TLS) polymerases that are able to replicate past DNA lesions. The PCNA interaction motif and/or the ubiquitin binding motif in most TLS polymerases seem to be important for the regulation of TLS. The TLS pathway is usually error-prone because TLS polymerases have low fidelity and no proofreading activity. PCNA can also be further polyubiquitinated by Ubc13/ Mms2/Rad5 complex, which adds an ubiquitin chain onto monoubiquitinated K164 of PCNA. PCNA polyubiquitination directs a different PRR pathway known as error-free damage avoidance, which uses the newly synthesized sister chromatid as a template to bypass DNA damage presumably through template switching mechanism. Mammalian homologues of all of the yeast PRR proteins have been identified, thus PRR is well conserved throughout evolution. Mutations of some PRR genes are associated with a higher risk for cancers in mice and human patients, strongly supporting the importance of PRR as a tumor suppressor pathway.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.6
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• pp.501-509
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• 2005

Ameloblastoma is a common odontogenic benign tumor of the jaw bone. However, it might be albe to infiltrate into the adjacent tissue, causing bony destruction and high recurrent rate. The aim of the study is to understand the biologic behavior of recurred ameloblastoma through immunohistochemical study. The PCNA, Ki-67, p53 and cytokeratin 17, cytokeratin 18 antibody staining were used. There was significant difference of positive reaction between non-recurred ameloblastoma and recurred ameloblastoma in PCNA and cytokeratin 17. There were no significant difference of positive reaction between non-recurred ameloblastoma and recurred ameloblastoma in p53, Ki-67 and cytokeratin 18. From the above results, it is suggested that the recurrence of ameloblastoma is related to positive reactions of PCNA and cytokeratin 17 and the progonsis of the recurrence of ameloblastoma is able to be predicted by using PCNA and cytokeratin 17.

• Korean Journal of Head & Neck Oncology
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• v.10 no.2
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• pp.200-205
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• 1994

Proliferating cell nuclear antgen(PCNA) plays an important role in DNA synthesis in nucleoli and is highly conserved non-histone nuclear protein composed of 261 amino acid. and is considered to correlated with the cells proliferative state, because it is synthesized particulary during the proliferative period of late Gland S-phase. Therefore, PCNA index meaningfully increases in the active or proliferative kinetic cells. By the use of recently developed monoclonal antibodies against PCNA, the immunohistochemical staining methods can make possible. These staining methods are the useful and productive one for ascertaining the cell's proliferating abillity. Moreover, immunohistochemical staining method with a antiPCNA antibody has particulrar advantages as follows. By means of these methods, we can stain the tissue that was already fixed in formalin or paraffin wax. We can see with naked eye that which cell is, where is differentiated through a microscope. Lastly, it maintains the whole tissue architecture and makes a search for the correlation. As we have seen above, the immunohistochemical staining methods for PCNA have been studied as an impotant factor that can find the cell proliferative kinetics in malignancy and biologic behavior of tumors. To investigate of the proliferative activity in thyroid nodule, Authors evaluated cell proliferative activity by immunostaing for PNCA in 45 pathologically confirmed solitary thyroid nodule. The results were as follows. 1) The benign nodules were 25 cases(Adenomatous Goiter: 20 cases, Follicular adenoma: 5 cases) and malignant nodules were 20 cases(Papillary Ca : 14 cases, Follicular Ca : 4 cases, Anaplastic Ca : 2 cases). 2) The Most prevalent age groups were 4th decade(11 cases), and the next group was 5th decade. 3) The average PCNA labelling indices were as follows. Adenomatous goiter(I6.9%), Follicular adenoma(37.6%), papillary Ca(26.3%), Follicular Ca(8.8%) and Anaplastic Ca(86.7%). There were no significant differences in benign(20.4) and malignant nodules (28.8%) except anaplastic Ca(p=0.3226). 4) When the average tumor size 2cm in papillary Ca, the PCNA indices were 26.0% (below 2cm) : 26.6% (above 2cm) (p=0.9642). The PCNA incidies were 23.9% (with lymphatic spread) : 28.7% (without lymphatic spread) (p=0.7056). There were no signlficant differences in the above cases. In conclusion, there were no significant differences in cell proliferative activity by staining for PCNA between benign and malignat nodules except anaplastic Ca.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5439-5444
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• 2012

Objective: To explore the correlation of human papillomavious (HPV) infection with expression of p53 and proliferating cell nuclear antigen (PCNA) in patients with different ethnicity in Xinjiang, China. Methods: 166 biopsy specimens from 83 laryngeal squamous cell carcinomas (LSCC), 63 laryngeal papillomas (LP), and 20 laryngeal inflammatory polyps (LIP) were included in this study. HPV infection was determined by polymerase chain reaction (PCR) using specific types of HPV primers. Expression of p53 and PCNA was assessed using immunohistostaining. Results: The frequency of HPV 6/11 was higher in LP (33.3%) than in LSCC (9.6%) (P<0.0005), whereas the frequency of HPV 16/18 was higher in LSCC (37.3 %) than in LP (6.3%) (P<0.0005). Patients of the Han ethnic group with LSCC had a higher infection rate with HPV 6/11 or HPV 6/11 and HPV 16/18 coinfection than those of Uygur and Kazak ethnicity (P<0.05). Overexpression of p53 and PCNA were higher in LSCC (62.7%, 57.8%) than in LP (38%, 33.3%) (P<0.005, and P<0.005, respectively). That of p53 was not associated with lymph-node metastases and clinical stages, but overexpression of PCNA closely correlated with clinical stage. Conclusions: These results strongly implicate HPV6/11 infection in the carcinogenesis of LSCC and LP, respectively. There was a higher coincidence of increased malignancy of laryngeal tumors with overexpression of p53 and PCNA. Overexpression of p53 may serve as an early risk marker for malignant transformation in HPV infected cells while the overexpression of PCNA may serve as a late marker for progression of LSCC.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.21-21
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• 2001

일반적으로 세포는 방사능이나 항암제 등의 자극에 의해 DNA가 손상받았을 때 DNA를 합성하기 전, DNA변이를 복구하기 위해 cell cycle을 정지시키게 된다. pRB(retinoblatoma protein)는 이러한 cell cycle의 조절기작에서 중요한 역할을 담당하는 것으로 알려져 있다. G1기에서 S기로 진행하는 것을 조절하는 단백질인 pRB 은 E2F(cell cycle transcription factor)와 상호작용하여 cell cycle 진행에 필요한 전사활성을 억제, PCNA (proliferating cell nuclear antigen)의 합성을 저해한다. 또한, E2F와 결합된 pRB는 apoptosis를 제어하는 유전자를 조절하는 것으로 알려져 있다. Cell cycle에 영향을 미치는 항암제의 일종인 busulfan을 처리하면, 정소 내에 존재하는 대부분의 생식세포들은 사멸되고 spermatogonia만 남는 것으로 알려져 있다. 그러나 그 기작에 대해서는 자세히 연구된 바가 없다. 본 연구에서는 busulfan처리시 spermatogonial stem cell이 어떤 기작에 의해 손상받지 않고 유지되는지를 알아보고자 실험을 수행하였다. Busulfan을 처리한 마우스 (항암제 투여 후 5주)와 정상적인 13주령의 마우스의 정소로부터 각각 세포를 분리하였다. LSC (laser scanning cytometry)를 이용하여 처리군(busulfan treated mice)과 대조군(normal mature mice)에 대해 각각 DNA함량을 비교ㆍ분석한 결과 G0/G1(2N)에 머물러 있는 세포비율이 처리군에서 현저하게 증가했다 (79.3$\pm$5.5%:8.1$\pm$1.3%). Cell cycle의 G1/S check point인 pRB와 PCNA 발현을 Western blot과 면역조직학적인 방법(immunohisto-chemistry)을 이용하여 조사하였다 PCNA는 대조군과 비교해, 처리군에서 매우 낮은 수준으로 발현되었다. 면역염색된 정소단면을 살펴보면, 대조군에서는 모든 세정관에서 PCNA를 발현하는 세포가 높은 비율로 검출되었고, 처리군에서는 소수의 세정관에서 세포들이 낮은 수준으로 검출되었다. 반면에, pRB의 경우 PCNA와는 상반된 결과를 나타내어, 대조군에서는 거의 발현이 되지 않는 반면, 처리군에서는 대부분의 세정관내, 기저막을 따라 위치한 세포들에서 발현되었다. 이상의 결과는 busulfan에 의해 pRB의 인산화가 억제, pRB 와 결합된 E2F는 전사 활성이 억제되어, PCNA 합성을 저해하는 것으로 설명되어질 수 있다. 결론적으로, 인산화가 억제된 pRB (underphosphorylated RB protein)이 quiescent spermatogonial stem cell에서만 특이하게 발현하는 단백질이며, 이러한 pRB의 발현은 apoptosis를 제어하는 역할을 담당해 busulfan처리에 의해 손상받지 않고 남아있는 것으로 시사된다.