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).
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.
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.
Since most ATCs were reported to carry the mutated form of p53, while PTCs carry mostly the wild-type form of p53, it is likely that FUCA1 expression levels are regulated, at least in part, by the p53 status in thyroid cancers.
Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers.
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.
Subgroup by ethnicity showed that there was no significant association between p53Arg72Pro polymorphism and thyroid cancer risk in both Caucasians and Asians.
Sequence analysis of Braf, Ret, Hras, Kras, Kit and Trp53, all genes that are commonly mutated in human thyroid cancers, did not show any evidence of mutation in the tumours.
These in vitro studies imply that p53 mutant reactivation by small compounds may become a novel anticancer therapy in undifferentiated thyroid carcinomas.
Instead, data obtained by cell transfection indicate that ΔNp73, a member of p53 family selectively expressed in thyroid carcinomas, plays a role in activating periostin gene expression.
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.
Concomitant aberration of FHIT gene and p53 could be responsible for development of highly malignant types of thyroid cancer and may be considered as a prognostic marker for these tumors.
When using retroviral-vector-based gene therapy, wild-type LTR vectors should be employed to target TP53-defective tumors, whereas thyroid-specific promoters should be used for transcriptional targeting of thyroid carcinomas carrying wild-type TP53.