• Journal of Chest Surgery
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• v.29 no.11
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• pp.1223-1231
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• 1996

Immunohistochemical stains for RB and p53 tumor suppressor gene products were performed on 72 cases of resected primary lung cancer tissues to study the correlation between their expressions and the histologic types, the clinical stage, and the survival rate. The results were as follows. 1. The RB protein was altered or absent in 38 cases (52.8%), and the mutant p53 protein was detected in 35 cases (48.6%). 2. The incidences of RB and p53 protein expression were significantly different among the histologic types (p＜0.05) but were not correlated with the clinical stages of lung cancer (p＞0.05). 3. The two year survival rate of patients with alteration of both RB and p53 genes (RB-/p53＋) was 22. 4%, and that with no alteration of both genes (RB+/p53-) was 63.1%. This difference was statistically significant (p=0.01). 4. It was shown that alteration of RB protein greatly affects the prognosis of lung carcinoma by multivariate analysis of prognostic factors. The presence or absence of RB and mutant p53 protein in tumor cells is closely related to the survival of primary lung cancer patients, and it is suggested that RB gene expression is an independent prognostic factor of primary lung cancer.

• BMB Reports
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• v.30 no.3
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• pp.205-210
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• 1997

p53 tumor suppressor plays an important role in the regulation of cellular proliferation. To identify proteins regulating the expression of p53 in rat liver, we analyzed p53 promoter by electrophoretic mobility shift assay (EMSA) and DNase I footprinting assay. We found that a protein binds the sequence CACGTG, bHLH consensus sequence in rat p53 promoter. Southwestern blotting analysis with oligonucleotides containing this sequence shows that the molecular weight of the protein is 100 kDa. This size is not compatible with the bHLH family such as USF or c-Myc/Max which is known to regulate the expression of the human and mouse p53 gene. Therefore this 100 kDa protein may be a new protein regulating basal transcription of rat p53. We purified this 100 kDa protein through sequence-specific DNA affinity chromatogaphy.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.169-173
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• 2001

Objectives: The p53 tumor suppressor gene encodes a nuclear transcription factor that is critical regulator of cell growth and proliferation through its action in cell-cycle checkpoint control. The wide variety of stressful stmuli which include DNA damage, hypoxia, heat shock, metabolic changes activate the p53 protein, which in turn drives a series of events that culminate either in cell cycle arrest or apoptosis. Mutations of the p53 gene is the most common genetic alteration in human cancer. This gene is altered in approximately 40-60% of head and neck cancers. Whereas the wild-type form of the p53 protein plays a central role in cell-cycle control in response to DNA damage, most of the mutant forms are unable to do so. The high levels of p53 protein expression in tissues are related to the increased cellular proliferative activity and may be associated with the poor clinical outcome. To determine whether the expression of the p53 protein has prognostic significance and is associated with patterns of treatment failure in head and neck squamous cell carcinoma (HNSCC), We analyzed p53 overexpression in 40 cases of HNSCC. Materials and Methods: Immunohistochemical analysis with a monoclonal antibody (DO7) specific for p53 protein was used to detect expression of the protein in formalin-fixed, paraffin-embedded tumor samples from 40 HNSCC. We evaluated p53 protein expression and analyzed the relationship between the p53 overexpression and age, sex, primary tumor site, stage, survival rate, recurrence. All reported P values resulted from two-sided statistical tests. Results: Overexpression of p53 was detected in 20 cases(50%) among 40 cases of HNSCC. The p53 overexpression was not associated with age, sex, primary tumor site, stage, recurrence and survival rate. Conclusions: In our results, p53 was not significant prognostic factor in HNSCC. Based on many previous studies, It is evident that p53 has a certain role in tumorigenesis of HNSCC. So, the further study is needed to evaluate the prognostic significance of p53 in HNSCC.

• Biomedical Science Letters
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• v.13 no.3
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• pp.213-221
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• 2007

This study was designed to investigate the correlation between the expression rate of p53 and p21 proteins, c-erbB-2 oncoprotein and $TGF-{\beta}1$ and tumor prognostic factors in colon cancer including the tumor size, histological differentiation and Dukes' stage. The expression rate of p53 protein was 11.4% (4 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation. In other words, the poorer differentiation, the higher the expression rate of p53 protein (P<0.05). The expression rate of p21 protein was 17.1% (6 cases) at well differentiation, 40.0% (14 cases) at moderately differentiation, and 8.6% (3 cases) at poorly differentiation, indicating that, as the histological malignant degeneration progressed, the expression rate of p21 protein decreased distinctively (P<0.05). However, the correlation of the above mentioned proteins with tumor size and Dukes' stage was not recognized. The expression rate of c-cerbB-2 oncoprotein was 11.4% (4 cases) at well differentiation, 54.3% (19 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation, indicating that the poorer differentiation, the higher expression rate of c-erbB-2 oncoprotein (P<0.05). The expression rate of $TGF-{\beta}1$ was 17.1% (6 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 11.4% (4 cases) at poorly differentiation. As Dukes' stage progressed, the expression rate of $TGF-{\beta}1$ was 8.6% (3 cases) in stage A, 20.0% (7 cases) in stage B, 37.1 % (13 cases) in stage C, and 11.4% (4 cases) in stage D. There was a difference in expression rates between Dukes' stages (P<0.05). In 10 cases, p53 protein was positive while p21 protein was negative, and in 6 cases, p53 protein was negative whereas p21 was positive (P<0.05). Therefore, a statistically significant inverse correlation between the expression rate of p53 protein and that of p21 protein was observed. In conclusion, since there was a signigicant correlation between histological differentiation of colon cancer and the expressions of p53 and p21 proteins and c-erbB-2 oncoprotein, and between Dukes' stage and the expression of $TGF-{\beta}1$, it was conformed that the overexpression of p53 and p21 proteins, c-erbB-2 oncoprotein, and $TGF-{\beta}1$ is closely associated with the occurrence of colon cancer and its progress. Accordingly, this study may be greatly beneficial to the presumption of diagnosis, treatment and prognosis of colon cancer patients.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1993.05a
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• pp.85-85
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• 1993

The clinical staging system for laryngeal cancers is not sufficient for prognosticator due to different biologic characteristics and their microenvironment according to primary sites. For determining the prognosticators, the authors peformed immunohistochemical staining to EGFR, p53 protein, and pRB in 40 cases of surgically treated squamous cell carcinomas of larynx in our institute during the past 5 years. The results are as followings; 1. The positive expression rate of p53 protein and negative expression rate of pRB showed correlations with clinical parameters. 2. The three-year survival rate for p53 protein positive cases was worse than the p53 protein negative cases. 3. Expression rate of EGFR was not correlated with the clinical parameters. As a conclusion, expression rates of p53 protein and pRB not only reflect well the biologic behavior of laryngeal cancer, but correlate closely with the tumor factors. Therefore they may be useful as the prognosticator to predict the malignant potency of laryngeal squamous cell carcinomas.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.221-229
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• 2001

Background: Inactivation of tumor suppressor genes is believed to be important in the development of many human malignancies. Recently, several lines of evidence have indicated that the wild type p53 gene located at 17p13.3, may function as a tumor suppressor gene and that a mutant p53 gene could promote transformation by inactivating normal p53 function in a dominant negative fashion. These broad spectrum of p53 mutation in human cancers provide that mutant p53 and their protein may be potential targets of tumor diagnostic and therapeutic interventions. Method: Colony formation was performed to investigate growth suppressional ability. p53 expression pattern was examined by western blot and p53-mediated transactivation ability was assessed by CAT activity. SNU C2A cells were observed in apoptotic aspects induced by etoposide and $H_2O_2$ treatment, detecting sensitivity on agent, DNA fragmentation through agarose gel, chromatin condensation by fluorescence microscope, and cell cycle distribution by FACS. Result: 1) p53 mutant his179arg ($histidine{\rightarrow}arginine$) detected in SNU C2A cells lost transcriptional activity and growth suppression ability, showing dominant negative effect on its wild type p53. 2) Etoposide-treated SNU C2A cells induced apoptosis, exhibiting dramatic reduction of cell growth, DNA fragmentation, nuclear condensation formation of apoptotic body and increment of sub-G1 cell fraction. 3) Etoposide and $H_2O_2$-treated SNU C2A cells have no high increase of p53 expression and overexpressed p53 protein changed localization, from cytoplasm to nucleus. Also, p53-mediated transcriptional activity was increased by agents-treatment. Conclusion: SNU C2A cells coexpress wild-type and mutant p53 protein induced apoptosis in the condition on DNA damage, through localizational shift from cytoplasm to nucleus of p53 protein rather than the induction of p53 protein. SNU C2A cells derived mutant p53 his179arg abrogated both the growth supression ability and transactivational activity, showing inhibition effect on transcriptional activity of wild type p53, but did not repress the activity of wild type p53 in SNU C2A cells owing to dominant activity of wild type. These cell condition may provide new gene therapeutic implications leading effective antiproliferation of cell when mutant and wild-type p53 protein were co-expressed in cell.

• Biomedical Science Letters
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• v.19 no.4
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• pp.348-352
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• 2013

microRNAs (miRNAs) play pivotal roles in controlling cell proliferation and differentiation. miRNA expression in human is becoming recognized as a new molecular mechanism of carcinogenesis. microRNA-34a (miR-34a), a member of the p53 network, was found to be regulated in multiple types of tumor. The purpose of this study was to define roles of miR-34a expression in cervical intraepithelial neoplasia with human papillomavirus infection, and its relationship with p53 protein expression. This study was performed to analyze expression of miR-34a by using qRT-PCR, and to evaluate p53 protein expression by using immunohistochemistry in 40 cases. Down-regulation of miR-34a expression was detected in 27 (67.5%) out of 40 cases and Immunoreactivity for p53 was found in 17 (42.5%) out of 40 cases. Nineteen (82.6%) of the 23 cases with a negative p53 expression showed a down-regulation miR-34a expression, there was a significant associations between miR-34a and p53 protein expression (P=0.04). These results suggest that miRNA-34a expression tend to be reduced depending on the advanced histologic grade, and down-regulation of miR-34a expression might be associated with inactivation of p53 protein expression by human papillomavirus infection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3723-3727
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• 2015

The p53 tumor suppressor protein is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage. p53 is a substrate for the ubiquitin-proteasome system, however, the ubiquitin-conjugating enzymes (E2s) involved in p53 ubiquitination have not been well studied. UBE2Q1 is a novel E2 ubiquitin conjugating enzyme gene. Here, we investigated the effect of UBE2Q1 overexpression on the level of p53 in the MDA-MB-468 breast cancer cell line as well as the interaction between UBE2Q1 and p53. By using a lipofection method, the p53 mutated breast cancer cell line, MDA-MB-468, was transfected with the vector pCMV6-AN-GFP, containing UBE2Q1 ORF. Western blot analysis was employed to verify the overexpression of UBE2Q1 in MDA-MB-468 cells and to evaluate the expression level of p53 before and after cell transfection. Immunoprecipitation and GST pull-down protocols were used to investigate the binding of UBE2Q1 to p53. We established MDA-MB-468 cells that transiently expressed a GFP fusion proteins containing UBE2Q1 (GFP-UBE2Q1). Western blot analysis revealed that levels of p53 were markedly lower in UBE2Q1 transfected MDA-MB-468 cells as compared with control MDA-MB-468 cells. Both in vivo and in vitro data showed that UBE2Q1 co-precipitated with p53 protein. Our data for the first time showed that overexpression of UBE2Q1can lead to the repression of p53 in MDA-MB-468 cells. This repression of p53 may be due to its UBE2Q1 mediated ubiquitination and subsequent proteasome degradation, a process that may involve direct interaction of UBE2Q1with p53.

• The Korean Journal of Cytopathology
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• v.7 no.2
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• pp.144-150
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• 1996

Although bladder cancers are very common, little is known about their molecular pathogenesis. It is known that p53 alteration is found in about 60% of muscle-invasive bladder cancer, necessiating aggressive therapy and poor outcome. We examined the nuclear expression of p53 protein, using D07 monoclonal antibody in the urine samples from 31 patients with transitional cell carcinoma of the bladder to investigate the correlation of p53 overexpression with histologic grades and depth of invasion. The positive rate of p53 protein was 27% in superficial bladder tumor, but increased up to 71% in the invasive bladder carcinomas. The overexpression of p53 protein increased according to Mostofi grading system from 18% in grade I, 45% in grade II, and up to 100% in grade III. The p53 expression tended to be higher in the invasive and high grade bladder cancers than in the superficial and low grade ones(p<0.05). These results suggest that immunohistochemical analysis of the urine specimen in the bladder cancer patients could be a useful method of screening for the presence of p53 mutant protein. The mutant p53 protein expression may be an indicator of bladder cancer with more proliferative potential and/or aggressive biologic behavior.

• Environmental Analysis Health and Toxicology
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• v.20 no.3 s.50
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• pp.229-235
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• 2005

태양광선,특히 자외선 B에 대한 환경적 노출은 편평세포암과 기저세포암을 포함하는 흑색선종 이외의 피부암과 크게 관련된다고 알려져 있다. 염기 류신 지퍼계 전사조절인자인 CChAT/enhancer binding protein-alpha는 표피 각질형성세포에서 다량으로 발현되었고, 각질형성세포의 증식을 억제하며 피부암 발생을 억제하는 유전자로서의 역할이 암시된 바 있다. 최근 자외선 B가 각질형성세포에서 p53에 의한 CCAAT/enhanrer binding protein-alpha의 발현을 강력하게 유도한다는 것이 보고되었다. 이러한 CCAAT/enhancer binding protein-alpha 단백질 발현의 유도는 세포 성장 억제 세포고사와 함께 일어났다. 이 연구는 glycogen synthase kinase-3 길항제가 자외선 B에 의한 CCAAT/enhancer binding protein-alpha 유도를 억제하며 변이 kinase-불활성 GSK의 강제 발현은 자외선 B가 CCAAT/enhancer binding protein-alpha전사조절부위 활성의 증가를 억제한다는 것을 보여주었다. 즉 자외선 B에 의한 CCAAT/enhancer binding protein-alpha의 유도가 p53과 활성 glycogen synthase kinase-3에 의한 것이라는 것을 증명하였다.