Evaluation of PTEN, PI3K, MTOR, and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma

Duman, Berna Bozkurt; Kara, Oǧuz; Uğuz, Aysum; Ateş, Berna Totan

doi:10.5114/wo.2014.43803

Cited by 14 publications

(18 citation statements)

References 39 publications

(59 reference statements)

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“…Through surgery and radioactive iodine ablation, most PTC patients have a good prognosis; however, a significant proportion of patients have persistent or recurrent disease and suffer from frequent recurrences or even distant metastases, leading to an unfavourable outcome. A minority of these patients will die from thyroid cancer ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

RDM1 gene overexpression represents a therapeutic target in papillary thyroid carcinoma

Huang

Sun

et al. 2017

Endocrine Connections

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RAD52 motif containing 1 (RDM1) encodes the RAD52 protein involved in DNA double-strand break repair and recombination events. However, the importance of RDM1 in papillary thyroid carcinoma (PTC) is largely unknown. In the present study, we examined the role of RDM1 in thyroid cancer. The RDM1 expression in PTC patients was examined using immunohistochemistry. The expression levels of RDM1 mRNA in thyroid cancer cells were measured by quantitative real-time PCR (qRT-PCR). Lentivirus-mediated small interfering RNAs (siRNAs) were used to knock down the RDM1 expression in the K1 and TPC1 cells. Then, changes in the RDM1 target gene expression were determined by qRT-PCR and Western blot. Cell proliferation was examined by a high content screening assay. Cell cycle distribution and apoptosis were detected by flow cytometric analysis and MTT analysis. We showed that the RDM1 expression was higher in PTC tissue compared to pericarcinous tissue. RDM1 mRNA was found to be expressed by qRT-PCR. Using a lentivirus-based RNA interference (RNAi) approach, the RDM1 expression was significantly inhibited. The inhibition of RDM1 expression by RNAi significantly impaired cell proliferation, increased apoptosis and arrested cells in the G2/M phase. These data showed that RDM1 was highly expressed in PTC tissue and thyroid cancer cell lines. Moreover, RDM1 may play an important role in cell proliferation, cell cycle distribution and apoptosis of human PTC cells.

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Section: Introductionmentioning

confidence: 99%

RDM1 gene overexpression represents a therapeutic target in papillary thyroid carcinoma

Huang

Sun

et al. 2017

Endocrine Connections

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“…The gene for PTEN protein lie in chromosome 10q23.3 area. PTEN protein is expressed in numerous early embryonic tissues, such as kidney, stomach, central and peripheral nervous system tissue (28). The expression levels of PTEN in the early stage of thyroid tissue growth and in adults are relatively high.…”

Section: Discussionmentioning

confidence: 99%

“…The expression levels of PTEN in the early stage of thyroid tissue growth and in adults are relatively high. In normal human cells, PTEN participates in the regulation of numerous signal transduction pathways, including PTEN/PI3K/AKT, FAK /PI30C and MAPK (28). Through these pathways, PTEN is involved in the maintenance of normal and regulatory substance metabolism and stabilization of the internal environment (29).…”

Section: Discussionmentioning

confidence: 99%

Cell penetrating peptide of sodium-iodide symporter effect on the I-131 radiotherapy on thyroid cancer

Fan

Liang

Liu

et al. 2017

Experimental and Therapeutic Medicine

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The aim of the present study was to clarify whether the cell penetrating peptide of sodium-iodide symporter (NIS) has an effect on the I-131 radiotherapy of thyroid cancer. Firstly, we combined the HIV-1 TAT peptide (a cell penetrating peptide, dTAT) and established a nanoparticle vector (dTAT NP) to study the delivery efficiency of this cell-penetrating strategy for tumor-targeted gene delivery. dTAT NP was transfected into cultured TPC-1 cells as a model to study the effects of I-131 radiotherapy on thyroid cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting results showed that the mRNA and protein expression levels of NIS in the transfected TPC-1 cells were substantially higher than in the negative control cells. MTT and flow cytometric analyses demonstrated that the cell growth and apoptosis rates of the TPC-1 cells were significantly inhibited and activated, respectively, by treatment with dTAT NP. The results of DAPI staining showed that treatment with dTAT NP visibly increased the nuclear apoptosis rate of the TPC-1 cells. The effect of dTAT NP on TPC-1 cells was associated with the promotion of caspase-3 and downregulation of the PI3K/Akt signaling pathway. In summary, the present data provide a pre-clinical proof-of-concept for a novel gene delivery system that efficiently delivers NIS to the targeted cancer cells and presents a satisfactory efficacy. This approach may offer an effective strategy for improving thyroid cancer gene therapy.

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“…PTEN inactivation reflected by complete absence of PTEN by IHC was seen in 24.5% of our PTC cohort. Previous studies have reported differences in incidence of PTEN in different ethnic group which range from 29.7% ( Duman et al , 2014 ) in Caucasian to 52.6% in Asian population ( Min et al , 2013 ). Our results were similar to the Caucasian population as compared with other ethnicities.…”

Section: Discussionmentioning

confidence: 99%

PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma

et al. 2015

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Background:PTEN gene at chromosomes 10q23.3 is a tumour suppressor gene that is inactivated in many types of human cancers. The known mechanisms of PTEN inactivation are rendered to mutation, epigenetic silencing by aberrant methylation or gene deletion. Although PTEN role has been documented in many cancers, PTEN alteration in papillary thyroid carcinoma (PTC) has not been fully elucidated. The aim of this study is to comprehensively investigate PTEN alterations in a large cohort of Middle Eastern papillary thyroid cancer by immunohistochemistry and fluorescent in situ hybridisation (FISH).Methods:PTEN protein expression was analysed by immunohistochemistry in a tissue microarray (TMA) format in a large cohort of more than 1000 patients with papillary thyroid cancer. Copy number changes in PTEN were analysed by FISH and data were correlated with clinicopathological parameters along with survival analysis.Results:PTEN inactivation reflected by complete absence of staining was seen in 24.5% of PTC samples, whereas PTEN deletion was seen only in 4.8% of the tested samples by FISH. No association was seen between PTEN loss of protein expression and PTEN gene deletion. However, interestingly, PTEN loss of expression was significantly associated with the follicular variant subset of papillary thyroid cancer.Conclusion:Our study confirmed that PTEN might have a role in pathogenesis in a subset of PTC. PTEN loss of protein expression is a more common event in follicular variant of papillary thyroid cancer. Lack of association between PTEN loss of protein expression and PTEN gene deletion might indicate that gene deletion may not be the sole cause for PTEN loss of expression and these results might raise the possibility of other mechanism such as promoter methylation-mediated gene silencing to be responsible for PTEN inactivation.

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Evaluation of PTEN, PI3K, MTOR, and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma

Cited by 14 publications

References 39 publications

RDM1 gene overexpression represents a therapeutic target in papillary thyroid carcinoma

RDM1 gene overexpression represents a therapeutic target in papillary thyroid carcinoma

Cell penetrating peptide of sodium-iodide symporter effect on the I-131 radiotherapy on thyroid cancer

PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma

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