• Journal of Life Science
• /
• v.16 no.1
• /
• pp.12-16
• /
• 2006

Genetic alternation of Brca1 predispose of breast and ovarian cancer. Brca1 plays critical role in cell cycle regulation following DNA damage. Previous studies revealed that Brca1 plays an important role in S phase and G2/M checkpoint regulation. However, whether Brca1 involves in spindle checkpoint is unclear. In this study, the role of Brca1 in cell cycle response following nocodazole, which is a reagent that depolymerizes microtubules and activates the spindle checkpoint, has been examined using wild type $p53^{-/-}\;and\;p53^{-/-}Brca1^{-/-}$ mouse embryonic fibroblasts (MEFs). While wild type and Brca1-proficient MEFs showed an acute mitotic arrest, Brca1-deficient MEFs failed to arrest at mitotic phase in response to nocodazole treatment. In double-thymidine block and nocodazole treatment experiment, a portion of $p53^{-/-}\;Brca1^{-/-}$ MEFs were clearly by-passed nocodazole induced mitotic arrest. Consistent with this, in morphologic analysis, $p53^{-/-}\;Brca1^{-/-}$ MEFs showed growing cell morphology after nocodazole treatment. Taken together, these results suggest that Brca1 protein is an important component for normal induction of spindlecheckpoint and impairment of Brca1 function could induce dysregulation of mitotic cell cycle that ultimately results in genomic instability.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.5
• /
• pp.1787-1791
• /
• 2012

Objective: The p53 tumor suppressor pathway plays an important role in gastric cancer (GC) development. Auto-regulatory feedback control of p53 expression is critical to maintaining proper tumor suppressor function. So far, several studies between p53 Arg72Pro polymorphism and GC have generated controversial and inconclusive results. Methods: To better assess the purported relationship, we performed a meta-analysis of 19 publications. Eligible studies were identified by searching the Pubmed database. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess any link. Results: Overall, a significant association was detected between the p53 Arg72Pro polymorphism and GC risk (Pro-allele vs. Arg-allele: OR = 1.05, 95%CI = 1.01-1.08; Pro/Pro vs. Arg/Arg: OR = 1.13, 95%CI = 1.04-1.22). Moreover, on stratified analysis by race, significantly increased risk was found for Asian populations (Pro-allele vs. Arg-allele: OR = 1.06, 95%CI = 1.02-1.10; Pro/Pro vs. Arg/Arg: OR = 1.16, 95%CI = 1.07-1.26; Pro/Pro+Pro/Arg vs. Arg/Arg: OR = 1.58, 95%CI = 1.09-2.27). Conclusions: Our study provided evidence that the p53 72Pro allele may increase GC risk in Asians. Future studies with larger sample size are warranted to further confirm this association in more detail.

• Research in Plant Disease
• /
• v.17 no.2
• /
• pp.216-221
• /
• 2011

A representative isolate KU53 of the predominant Penicillium species was obtained from rice samples from rice processing complexes of National Agricultural Cooperative Federation in Korea. In this study, isolate KU53 was identified by its morphological and molecular characteristics. The macro- and microscopic characteristics of isolate KU53 were compared with the P. fellutanum reference isolate KCTC16913 on different media; isolate KU53 was generally identical to those of the reference isolate KCTC16913. In a molecular-based identification, the ${\beta}$-tubulin and translation elongation factor 1-alpha sequences of isolate KU53 was most closely related to those of P. fellutanum. Thus, isolate KU53 from stored rice could be identified as P. fellutanum, some isolates of which are known to produce mycotoxin-related metabolites. To our knowledge, this is the first detection of P. fellutanum from stored rice in Korea.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.9
• /
• pp.4477-4479
• /
• 2012

Background: The high incidence and relatively good prognosis of breast cancer has made it the most prevalent cancer in the world today. A large number of distinct mutations and polymorphisms in the p53 gene have been reported worldwide, but there is no report regarding the role of this inherited susceptibility gene in breast cancer risk among the Bengalee Hindu Caste females of West Bengal, India. Aim of the Study: We investigated the distribution and the nature of p53 gene mutations and polymorphisms in exons 5-7 in a cohort of 110 Bengalee Hindu breast cancer patients and 127 age, sex and caste matched controls by direct sequencing. Results: We did not observe any mutations and polymorphisms in our studied individuals. Conclusion: We therefore conclude that mutations in exons 5-7 of p53 gene are rare causes of breast cancer among Bengalee Hindu caste females, and therefore of little help for genetic counseling and diagnostic purposes.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.12
• /
• pp.7439-7444
• /
• 2013

Aim: ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. Methods: In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Results: Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Conclusion: Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

• Journal of the Korean Magnetic Resonance Society
• /
• v.22 no.3
• /
• pp.64-70
• /
• 2018

Human Tid1, belonging to the family of the Hsp40/DnaJ, functions as a co-chaperone of cytosolic and mitochondrial Hsp70 proteins. In addition, the conserved J-domain and G/F-rich region of Tid1 has been suggested to interact with the p53 tumor suppressor protein, to translocate it to the mitochondria. Here, backbone NMR assignments were achieved for the putative p53-binding domain of Tid1. The obtained chemical shift information identified five ${\alpha}$-helices including four helices characteristic of J-domain, which are connected to a short ${\alpha}$-helix in the G/F-rich region via a flexible loop region. We expect that this structural information would contribute to our progressing studies to elucidate atomic structure and molecular interaction of the domain with p53.

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

• The Korean Journal of Zoology
• /
• v.38 no.2
• /
• pp.204-211
• /
• 1995

In an effort to develop a new therapeutic strategy for human gene therapy of solid ovarian tumor, we studied the expression of the p53 tumor suppressor Sene as well as regulatory subunits of cyclic AMP (cAMP)-dependent protein kinase in human ovarian carcinoma cells. Four cell lines (2774, Caov-3, SK-OV-3 and OVCAR-3) were selected for the analyses. The p53 transcript and protein were detected only in the 2774 cell line by Northern and Western Bnalysis. In the relatively fast growing cell line, SK-OV-3, the %rope 1 a regulstorv subunit (RIA of CAMP-dependent protein kinase was the highest among the four cell lines. The expression level of $RII\beta$ protein was low in the four cell lines examined. These results maw point to a direction to select the target gene(sl to be employed for gene therapy to control the ovarian cancer.

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

• Tuberculosis and Respiratory Diseases
• /
• v.63 no.3
• /
• pp.251-260
• /
• 2007

Purpose: An imbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis. Capase 3, survivin and p53 have been identified as important members of the apoptotic related proteins. This study evaluated the proliferating cell nuclear antigen(PCNA), apoptosis, apoptotic related protein such as capase 3, survivin and p53 using urethane-induced mouse lung carcinogenesis, which provides reproducible steps from hyperplasia to adenocarcinoma. Methods: Urethane was administered to the ICR mice through an intra-peritoneal injection, The mice were sacrificed at 5, 15, and 25 weeks after urethane intervention. The sequential morphological changes and immunohistochemical expression of PCNA, apoptosis, capase 3, survivin, and p53 were examined during mouse lung carcinogenesis. Results: During carcinogenesis, the sequential histological changes were observed from hyperplasia of type II pneumocytes, to anadenoma, and ultimately to an overt adenocarcinoma. The PCNA Labeling index (LI) was 9.6% in hyperplasia, 23.2% in adenoma, and 55.7% in adenocarcinoma, respectively. The apoptotic LI was 0.24% in hyperplasia, 1.25% in adenoma, and 5.27% in adenocarcinoma. A good correlation was observed between the PCNA LI and apoptotic LI. The expression of caspase 3 was remarkable- i.e., 46.7% in adenocarcinoma, in contrast to 15% in hyperplasia and 16% in adenoma. Survivin was detected weakly in the alveolar hyperplasia and showed an increasing expressional pattern in adenoma and adenocarcinoma. p53 expression was detected only in the adenocarcinoma lesions with an expression rate of 13.3%. The level of caspase 3 expression correlated with the increase in the apoptotic index. The positive expression of caspase 3 was associated with an increased apoptotic index. Conclusions: These results suggest that the PCNA LI and apoptotic LI might be useful markers for evaluating the risk of a malignant transformation. In addition, caspase, survivin and p53 might play a role in the early and late steges of urethane-induced mouse lung carcinogenesis.