• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.305-309
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• 2016

PTEN protein is an important tumour suppressor factor detectable by immunohistochemistry. The goal of the present study was to investigate the prognostic role of PTEN gene expression focusing on length of survival in breast cancer patients. This descriptive-analytical study was conducted on 100 breast cancer cases referred to Sabzevar hospitals in the north east of Iran between 2010 and 2011, followed up to 2015. The PTEN gene expression of tumour tissue samples was determined using specific monoclonal antibodies. The data were analyzed using Chi-square test and Fisher's exact test. Patient length of survival was analyzed after 4 years of follow-up using the Cox regression model. The PTEN gene was expressed in 70 of 100 samples, while being found at a high level in all noncancerous samples. There was an inverse significant relationship between expression of PTEN and tumour stage and grade (p<0.001). In addition, expression of PTEN in invasive ductal tumours was less than in non-invasive tumours. There was also an inverse significant relationship between the likelihood of death and PTEN gene expression (p<0.01). These findings indicate that lack of PTEN gene expression can be sign for a worse prognosis and poor survival in breast cancer.

• Molecules and Cells
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• 제38권11호
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• pp.959-965
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• 2015

Inducible and reversible gene silencing in desired types of cells is instrumental for deciphering gene functions using cultured cells or in vivo models. However, efficient conditional gene knockdown systems remain to be established. Here, we report the generation of an inducible expression system for short hairpin RNA (shRNA) targeted to PTEN, a well-documented dual-specificity phosphatase involved in tumor suppression and ontogenesis. Upon induction by doxycycline (DOX), the reverse tetracycline transcriptional activator (rtTA) switched on the concomitant expression of GFP and a miR-30 precursor, the subsequent processing of which released the embedded PTEN-targeted shRNA. The efficacy and reversibility of PTEN knockdown by this construct was validated in normal and neoplastic cells, in which PTEN deficiency resulted in accelerated cell proliferation, suppressed apoptosis, and increased invasiveness. Transgenic mice harboring the conditional shRNA-expression cassette were obtained; GFP expression and concurrent PTEN silencing were observed upon ectopic expression of rtTA and induction with Dox. Therefore, this study provides novel tools for the precise dissection of PTEN functions and the generation of PTEN loss of function models in specific subsets of cells during carcinogenesis and ontogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4527-4531
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• 2016

Background: PTEN protein is one of the most important tumour suppressor factors which is detectable by immunohistochemistry. The goal of the present study was to investigate the prognostic role of PTEN gene expression in breast cancer patients. Materials and Methods: This descriptive-analytical study was conducted on 100 breast cancer patients referred to Sabzevar hospitals in the north-east of Iran between 2010 and 2011, who were followed up to 2015. PTEN gene expression in tissue samples was determined using specific monoclonal antibodies and data were analyzed using Chi-square test and Fisher's exact test. Patient survival was analyzed after 4 years of follow-up using the Cox regression model. Results: PTEN gene expression was evident in 70 of 100 cnacer samples but was found at high levels in all non-cancer samples. There was an inverse significant relationship between PTEN gene expression and tumour stage or tumour grade (p<0.001). The expression of PTEN in invasive ductal tumours was lower than in non-invasive tumours. There was also an inverse significant relationship between the hazard of death and PTEN gene expression (p<0.001). In addition, there was an inverse significant relationship between tumour stage and hazard of death (p<0.001). Conclusion: These findings indicate that lack of PTEN gene expression can be a sign of a worse prognosis and poor survival in breast cancer cases.

• 대한골관절종양학회지
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• 제17권1호
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• pp.23-29
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• 2011

목적: 본 연구에서는 골육종 세포내 PTEN 발현정도가 세포 성장과 트로글리타존에 대한 반응도에 미치는 영향에 대해 알아보고자 하였다. 대상 및 방법: 웨스턴 블롯 분석을 통해 트로글리타존 처리 후 PTEN 발현 정도를 관찰하였고, WST를 통해 세포 증식정도를 측정하였다. 야생형 PTEN 및 돌연변이형 PTEN 발현시키는 플라스미드 DNA를 트랜스펙션하여 PTEN 발현 정도를 측정하였다. 결과: 사람골육종 세포주 U-2OS는 트로글리타존 처리 농도 및 시간에 비례하여 증식 억제를 보였고, 세포내 PTEN 발현 정도는 트로글리타존 처리 농도에 비례하여 증가하였다. 트로글리타존을 이용하여 U-2OS세포 내 PTEN 발현을 증가시키면 세포 성장 억제와 세포사 유도가 나타났다. 또한 플라스미드 트랜스펙션에 의한 PTEN 과발현은 트로글리타존의 세포증식 억제 효과를 증가 시키며 돌연변이형 PTEN을 트랜스펙션 시키는 경우 세포증식효과는 관찰되지 않았다. 결론: 골육종 세포내 PTEN 과발현이 트로글리타존에 의한 골육종 세포의 증식 억제 및 세포사 유도와 관련 되어있음을 알 수 있으며, 세포내에 PTEN이 과발현 된 상태에서 트로글리타존의 효과가 증가됨을 알 수 있었다.

• Journal of Chest Surgery
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• 제36권11호
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• pp.852-857
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• 2003

배경: 중피종은 일반적 치료에 대하여 큰 효과가 없다고 알려져 있다. 저자들은 Adenoviral p53에 민감하게 반응하는 중피종 세포주인 염증 및 표피세포 아유형(subtype)에 adenovirus유전자 핵산전달감염(transfection)으로 중피종 치료의 새로운 방법에 대하여 평가하고자 하였다. 대상 및 방법: 두 쌍의 adenoviral PTEN와 LacZ (Ad/GT-LacZ와 Ad/GV16) 매개체(vectors)에 REN (p53 sensitive)인 중피종 세포주(methothelioma cell lines)의 형질을 도입(transduction)하였으며, 단백질 함량은 Western blotting 분석을 이용하여 측정하였다. 세포사멸은 fluorescence-activated cell sorter analysis of subdiploid populations에 의하여 평가하였으며, 세포 생존력은 XTT 분석에 의하여 결정하였다. 통계 분석은 analysis of variance와 Student t test를 이용하여 하였다. 결과: Adenoviral PTEN 유전자로 처치된 세포사는 72시간 후에 MOI of 20에서 대조군 2.5%에 비하여 REN군 32.9%로 상대적으로 높게 나타났다. 또한 REN cell에서의 전구세포사멸 단백질(proapoptotic protein)인 BAX 발현 증가를, BCL-2에서 발현 감소를 나타내었으나, BCL-XL, BAK 및 BAD 단백질은 변화가 없었다. 결론: Adenovirus PTEN을 매개로 한 BAX 발현 증가는 세포사멸을 유도하고 p53에 민감한 중피종 세포들(p53-sensitive methothelioma cells)에서 세포 생존력을 감소시킨다. 이러한 결과는 PTEN 유전자 핵산전달감염하는 것은 중피종 치료의 새로운 대안적 방법이 될 수 있다는 것을 암시한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.17-24
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• 2014

Gastric cancer is highly invasive, aggressively malignant, and amongst the most prevalent of all forms of cancer. Despite improved management strategies, early stage diagnosis of gastric cancer and accurate prognostic assessment is still lacking. Several recent reports have indicated that the pathogenesis of gastric cancer involves complex molecular mechanisms and multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes. Functional inactivation of the tumor suppressor protein PTEN (Phosphatase and Tensin Homolog) has been detected in multiple cases of gastric cancer, and already shown to be closely linked to the development, progression and prognosis of the disease. Inactivation of PTEN can be attributed to gene mutation, loss of heterozygosity, promoter hypermethylation, microRNA- mediated regulation of gene expression, and post-translational phosphorylation. PTEN is also involved in mechanisms regulating tumor resistance to chemotherapy. This review provides a comprehensive analysis of PTEN and its roles in gastric cancer, and emphasizes its potential benefits in early diagnosis and gene therapy-based treatment strategies.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4521-4524
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• 2015

Background: Endometrial carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in Iranian women after breast, colorectal and lung cancers. Various genetic alterations appear to be early events in the pathogenesis of endometrial carcinoma and it seems that PTEN is the most commonly mutated gene in the endometrioid subtype. The aim of the present study was to investigate the correlation between mutations in exon 7 of PTEN gene and endometrial carcinoma. Materials and Methods: Seventy-five patients with endometrial carcinoma and 75 females whose underwent hysterectomy for non tumoral indication were selected for evaluation of PTEN mutations in exon 7 by PCR-SSCP and sequencing. Correlations between the frequency and type of mutation and the pathologic findings of the cancer (tumor subtype, stage and grade) were assessed. Results: All of the samples were obtained from Iranian patients. 60 % (45 cases) of the tumors were endometriod and 40% (30 cases) were of serous type. The grade distributions of the 75 cases according to the FIGO staging system were as follows: low grade, 20 cases; high grade 55 cases, low stage, 41 cases; high stage 34 cases. For exon 7 of the PTEN gene, the analysis showed that there were no mutations in our cases. Conclusions: Our findings in the present study suggest that exon 7 of PTEN does not play any significant role in the development of endometrial carcinoma in Iranian cases.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2199-2203
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• 2016

One of the most common cancer types faced by the women around the world is breast cancer. Among the several low, moderate and high penetrance genes conferring susceptibility to breast cancer, PTEN is one which is known to be mutated in many tumor types. In this study, we predicted and analyzed the impact of three deleterious coding non-synonymous single nucleotide polymorphisms rs121909218 (G129E), rs121909229 (R130Q) and rs57374291 (D107N) in the PTEN gene on the phenotype of breast tumors using computational tools SIFT, Polyphen-2, PROVEAN, MUPro, POPMusic and the GETAREA server.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제20권1호
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• pp.65-70
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• 2017

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is one of the phosphatase and tensin homolog hamartoma tumor syndrome with a PTEN gene mutation. It is a rare dominant autosomal disorder characterized by cutaneous lipomas, macrocephaly, intestinal polyps, and developmental delay. Diagnosing this syndrome is important, because it may represent the pediatric phenotype of Cowden syndrome, in which there is an increased risk for malignant tumors in children. Until now, the prevalence of BRRS is unknown. Several dozen cases have been reported in the medical literature, but no case has been reported in Korea. Here we report a case of a 19-year-old girl who was diagnosed with BRRS because of macrocephaly, intellectual disability, and intestinal polyps. Her mother had similar findings and a PTEN mutation. Neither patient had mutations detected by conventional mutation-detection techniques, but a PTEN gene deletion was demonstrated by chromosomal microarray analysis.

• Molecules and Cells
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• 제41권6호
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• pp.532-544
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• 2018

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.