scholarly journals Expression of transcription and growth factors and the AKT/m-TOR signaling pathway components in papillary thyroid cancer

2018 ◽  
Vol 64 (4) ◽  
pp. 208-215
Author(s):  
Liudmila V. Spirina ◽  
Sventlana Yu. Chizhevskaya ◽  
Irina V. Kondakova

Background: The molecular mechanism of thyroid cancer development is associated with changes in expression of transcription factors and growth factors accompanied by modified level of the AKT/m-TOR components. Aims. The aim of study was to determine NF-κB p65, NF-κB p50, HIF-1α, HIF-2α, VEGF, CAIX, VEGFR2 expression and mRNA level of the AKT/m-TOR signaling pathway components in papillary thyroid cancer compared to those in benign lesions. Material and methods: Forty patients aged 33—66 years with T1-4N0-2M0 papillary thyroid cancer (7 males and 33 females) were enrolled in the study. The mean age was 52.0±2.6 years. The comparison group included patients with benign lesions of thyroid tissue (4 males and 18 females) aged 38—66 years (mean age, 53.0±4.4 years). Expression levels of NF-κB p65, NF-κB p50, HIF-1α, HIF-2α, VEGF, CAIX, VEGFR2, and the AKT/m-TOR signaling pathway components were determined by RT-PCR using specific primers. Results: Increased expression of transcription factors NF-κB and HIF-2α was found in papillary thyroid cancer. The levels of AKT and PTEN mRNA were elevated in transformed tissues. c-Raf expression was reduced 2.1-fold in cancer compared to that in thyroid tissues with benign lesions. Multiple positive correlations were revealed between transcription and growth factors and the AKT/m-TOR signaling pathway components in cancer. An association between PTEN expression and the NF-κB mRNA level was revealed, being a sign of deregulation in the signaling cascade in cancer tissues. Conclusions: Overexpression of NF-κB, HIF-2α, AKT, PTEN and reduction of c-Raf expression is typical of thyroid papillary cancer.

2019 ◽  
Vol 65 (4) ◽  
pp. 608-613
Author(s):  
Lyudmila Spirina ◽  
Svetlana Chizhevskaya ◽  
Irina Kondakova ◽  
Yevgeniy Choynzonov

One of the initiating mutations in the development of thyroid cancer is BRAF-V600E, which leads to the various signaling cascades activation and changes in the production of transcription and growth factors. It is known that papillary thyroid cancer is characterized by activation of the expression of transcription factors NF-kB and HIF-2a and AKT/m-TOR signaling cascade. However, the relationship of the studied molecular markers in patients with the wild and mutant BRAF gene has not yet been studied. The aim of the work was to study the expression of transcription factors NF-65B p65 and NF-kB p50, HIF-1a, HIF-2a, growth factors VEGF, CAIX and VEGFR2, components of the AKT/m-TOR signaling pathway in patients with thyroid papillary cancer depending on the presence of mutations BRAF-V600E. Material and methods. It was included 40 patients with papillary thyroid cancer with the stage of the tumor process T1-4N0-2M0. The expression of the indicators was determined by real-time PCR. BRAF-V600E mutation was revealed by allele-specific PCR in real-time. Results and discussion. It was found that patients with the absence and presence of the BRAF-V600E mutation had similar clinical and morphological parameters of the disease, which was accompanied by a change in the molecular-biological characteristics of the tumor. The presence of the mutant form of the gene in the tumor led to a decrease in the AKT, cRAF, GSK-3P kinases mRNA levels and the overexpression of NF-kB p65, HIF-1 and VEGF. Conclusion. Patients with papillary thyroid cancer have no differences in the clinical and morphological characteristics of the disease, depending on the status of the BRAF-V600E gene, is characteristic. It was identified biological parameters associated with this somatic mutation. An increase in the mRNA level of growth and transcription factors was observed with a decrease in the activity of the AKT / m-TOR signaling pathway.


2021 ◽  
Vol 67 (1) ◽  
pp. 117-122
Author(s):  
Lyidmila Spirina ◽  
Svetlana Chizhevskaya ◽  
Irina Kondakova ◽  
Evgeny Choynzonov ◽  
Irina Kovaleva

Introduction. The oncosuppressor protein VHL plays a decisive or at least important role in the mechanisms of tumor progression. The development of malignant neoplasms of the thyroid gland is associated with the activation of transcriptional and growth factors. However, the role of the VHL gene in the mechanisms of the development of thyroid cancer has hardly been studied. The study aimed to study the clinical and morphological features, expression of transcription, growth factors, and components of the AKT / m-TOR signaling pathway in patients with papillary thyroid cancer depending on the level of expression of the VHL gene. Material and methods. The study included 46 patients with tumor pathology of the thyroid gland: 20 patients with benign thyroid tumors and 26 patients with papillary thyroid cancer T1-4N0-2M0. The expression of parameters was determined by PCR in real-time. Mutation BRAF-V600E was determined in allele-specific PCR in real-time. Results and their discussion. The mRNA level of the VHL gene remained virtually unchanged in the tissue of papillary cancer and benign thyroid tumors. It depended on the prevalence of the disease, the defeat of regional lymph nodes, and the BRAF-V600E status. In the presence of the BRAF-V600E mutation, VHL expression increased 615 times in patients with a mutation compared with patients without this somatic mutation. It was revealed that the expression of NF-κB p65, NF-κB p50, HIF-1, HIF-2, growth factors VEGF and CAIX in patients in the group with a VHL level> 1.0 RU increased compared with patients with a VHL level <1.0 RU. A decrease in PDK, c-RAF, mTOR, 70s 6 kinase, PTEN mRNA levels were also recorded in patients with increased levels of VHL expression compared with patients with VHL expression <1.0 RU. Conclusion. That the association of the VHL expression with tumor progression in papillary thyroid cancer and the mutant protein bRAF presence was found. Also, associations between the VHL expression and the level of mRNA of transcription and growth factors are noted.


2019 ◽  
Vol 10 (4) ◽  
pp. 3178-3181
Author(s):  
Punitha S ◽  
Vedha pal jeyamani ◽  
Sindhu S ◽  
Bhuvaneshwari P ◽  
Arshath A

Thyroid carcinoma is the majority widespread endocraine malignancy in that papillary thyroid cancer is a well-differentiated type. Since hyperthyroidism protects from thyroid cancer due to lack of reproduction of thyroid tissue by the thyroid-stimulating hormone. The papillary carcinoma is the fast-growing and metastases to local region rapidly. A 60 years old post menopausal women with a known case of hypertension of past 6 years on treatment and with hyperthyroidism of past 2 months was presented in the outpatient department in the hospital with chief complaints of mass in the neck with dyphagia, cough, breathlessness, sense of fullness and odynophagia of past 2 weeks. On physical and general examination patient found with diffuse thyroid swelling with enlarged right sided lymph node. The patient was diagnosed with papillary thyroid caricinoma with various investigation reports includes CT Scan, Immouno history chemistry reports, Histopathology and Two fine-needle aspiration biopsies. The patient has undergone 6 cycles of chemotherapy with the corticosteroids, anti-cancer drugs which includes Vincristine, Cyclophosphamide, Doxorubicin, anti- emetic drugs and also with H2 receptor blockers. The papillary thyroid cancer is common and occurs predominantly in females than in males and with good prognosis and decreased death rates. The higher level of thyroid function is very rare in case of PTC.


2021 ◽  
Vol 12 (9) ◽  
pp. 2777-2786
Author(s):  
Nannan Lv ◽  
Fei Liu ◽  
Lan Cheng ◽  
Feng Liu ◽  
Jinsong Kuang

Meta Gene ◽  
2020 ◽  
Vol 24 ◽  
pp. 100704
Author(s):  
Elham Amjad ◽  
Solmaz Asnaashari ◽  
Babak Sokouti

2021 ◽  
Vol 74 (8) ◽  
pp. 1925-1930
Author(s):  
Nataliia S. Pidchenko ◽  
Mykola V. Krasnoselskyi ◽  
Nataliia A. Mitriaieva ◽  
Lidiya V. Grebenik ◽  
Olha M. Astapieva ◽  
...  

The aim is to study the level of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2) in the blood serum of patients with papillary thyroid cancer, depending on the main clinical and morphological features of the disease. Materials and methods: The material was the information about 60 patients with papillary thyroid cancer (group 1). In group 2 there were 10 patients without oncopathology. All patients underwent clinical examination after total thyroidectomy before special treatment (radioiodine therapy): ultrasound diagnosis of the neck, confirmed diagnosis of papillary thyroid cancer by morphological examination of operative material. All patients underwent anthropometric studies (height, weight), on the basis of which the body mass index (BMI) was calculated. The study program also included determination of the level of thyroid-stimulating hormone of the pituitary gland (TSH), thyroglobulin (TG), antibodies to thyroglobulin (AB-TG). It was also determined the serum glucose level. In order to assess insulin resistance, the HOMA-IR index was calculated. All patients were tested for serum IGF-1 and IGF-2. Results: In the blood serum of patients with papillary thyroid cancer in 63% of patients the level of IGF-1 and in 85% – IGF-2 was probably higher than in the control group. There is a relationship between the level of IGF-1, IGF-2 and elevated level of proliferating factor – insulin in the serum of patients with papillary thyroid cancer. This may indicate an aggressive potential of the disease (i.e. clinical data on the prevalence of papillary thyroid cancer coincide with laboratory data). There was found a relationship between the expression of IGF-1, IGF-2 and insulin: at elevated levels of insulin> 24.9 μIU/ml, IGF-1 increases 4.2 times, and IGF-2 – 2.5 times. Evaluation of the relationship between the level of IGF-1 and IGF-2 and cervical lymph node involvement shows that in the absence of lesion (N0) there is an increase in these indicators by 2.2 and 1.8 times, respectively. Conclusions: The signaling system of insulin-like growth factors (IGF-1 and IGF-2) plays an important role in the occurrence and progression of malignant tumors. It is especially true for papillary thyroid cancer, so its components can be considered as potential diagnostic and prognostic markers of the disease and targets for anticancer therapy.


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