Based on our recommendations, we systematically characterized all new cell lines that we generated by a standardized approach that included (1) determination of human origin, (2) exclusion of lymphoma, (3) DNA fingerprinting and histological comparisons to establish linkage to presumed tissue of origin, (4) examining thyroid differentiation by screening two to three thyroid markers, (5) examination of biological behavior (growth rate, tumorigenicity), and (6) presence of common thyroid cancer genetic changes (TP53, BRAF, PTEN, PIK3CA, RAS, TERT promoter, RET/PTC, PAX8/PPARγ, NF1, and EIF1AX).
In this review, we provide an update on the current knowledge of the role of p53 family proteins in thyroid cancer and their possible use as a therapeutic target for the treatment of the most aggressive variants of this disease.
The resulted showed that MG132 induced significant apoptosis, and caused the accumulation of p53 protein in both p53 wild-type and mutant-type thyroid cancer cell lines, whereas the proapoptotic targets of p53 were transcriptionally upregulated only in the p53 wild-type cells.
Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer.
This study aimed to investigate the expression of p53 and BTG2 genes following 131I therapy in thyroid cancer cell line SW579 and the possible underlying mechanism.
It is evident from our study that Arg72Pro SNP of TP53 gene is connected with higher susceptibility to thyroid cancer especially in young age group, female gender, non-smokers and patients with elevated TSH levels, hence, implicated in thyroid carcinogenesis.
We found that, in an Rb(+/-) background promoting pituitary and thyroid tumors, decreased Mdm4 levels improved the survival of mice expressing wild-type p53, but not that of mice expressing p53(ΔP), a p53 hypomorph lacking the proline-rich domain.
Subgroup by ethnicity showed that there was no significant association between p53Arg72Pro polymorphism and thyroid cancer risk in both Caucasians and Asians.
Prkar1a(+/-) Trp53(+/-) mice developed more sarcomas than Trp53(+/-) mice (P < 0.05) and Prkar1a(+/-) Rb1(+/-) mice grew more (and larger) pituitary and thyroid tumors than Rb1(+/-) mice.
Orthotopic implantation with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck masses, with histopathologic features of a high-grade neoplasm (anaplasia, necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal invasion, lymph node and distant metastases) and immunoprofile of follicular thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8, and for cytokeratins.
As such, this article addresses the following aspects of intragenic mutations in thyroid cancer: thyroid stimulating hormone receptor and guanine-nucleotide-binding proteins of the stimulatory family mutations in hyperfunctioning tumors; mutations in RAS and other genes and aneuploidy; PAX8-PPARgamma rearrangements; BRAF mutations; mutations in oxidative phosphorylation and Krebs cycle genes in Hürthle cell tumors; mutations in succinate dehydrogenase genes in medullary carcinoma and C-cell hyperplasia; and mutations in TP53 and other genes in poorly differentiated and anaplastic carcinomas.
At variance with other human malignancies, p53 mutations are not frequent in thyroid cancer and are believed to be responsible mainly for cancer progression to poorly differentiated and aggressive phenotype. p63 and p73, two proteins with a high degree of homology with p53, are overexpressed in thyroid cancer, but their role in cancer initiation or progression is controversial.
These results provide evidence that p53 polymorphism is implicated in thyroid carcinogenesis and that individuals harboring the Pro/Pro genotype have an increased risk of developing thyroid cancer.