[Show abstract][Hide abstract] ABSTRACT: Papillary thyroid carcinoma (PTC) is common in Kuwait. The activation of the RET oncogene by DNA rearrangement (RET/PTC) is known to have an important role in PTC carcinogenesis. However, the real frequency of the RET/PTC expression in PTC is variable between different studies. This study seeks to determine the prevalence of RET/PTC and to analyze the RET oncogene expression associated with PTC in Kuwait.
RET expression and DNA rearrangements (RET/PTC 1, RET/PTC 2 and RET/PTC 3) were studied by RT-PCR in different thyroid diseases. Results were confirmed by the Southern blot and by immunohistochemistry. Quantitative real-time PCR was used to determine the level of RET mRNA expression in PTCs.
Wild-type (nonrearranged) c-RET oncogene was overexpressed in 60% of PTC cases and absent in follicular thyroid carcinoma (FTC), anaplastic thyroid carcinoma (ATC), follicular adenomas (FA) or normal thyroid. No RET/PTC rearrangement was detected in any sample. The c-RET expression in Hashimoto's thyroiditis and multinodular goiter was limited to follicular cells with PTC-like nuclear changes.
The overexpression of wild-type c-RET is a characteristic molecular event of PTCs in Kuwait. The prevalence of RET/PTC is zero and among the lowest recorded in the world.
Experimental and Molecular Pathology 10/2010; 90(1):61-5. · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been shown that increased estrogen can down-regulate its receptor, but there is no data to determine if that mechanism acts in the fetal brain as a consequence of high maternal estrogen levels. The aim of this study was to explore the expression of estrogen receptor (ER) in the developing fetal brain at 16, 19 and 21 days gestation (dg). The results revealed that both ERalpha and ERbeta isoforms, and some of their variants, were present in rat fetal brain at the transcript level and at the protein level. PCR results showed that the amount of ERalpha and ERbeta mRNA did not change significantly between 16, 19 and 21 dg; however, changes in protein expression were apparent. Two bands were detected for ERalpha protein by immunoblotting: the expression of the 73 kDa band, relative to the expression of actin, decreased significantly between 16 and 21 dg, while expression of the 67 kDa band did not change. Multiple variants of ERbeta were detected, including wild type ERbeta, ERbeta2 and ERbetaDelta5; the amounts of all decreased significantly, relative to the amount of actin, between 16 and 21 dg. A decrease in protein expression of some of the ER variants without an equivalent decrease in the amount of mRNA suggests that high levels of estrogen might triggered posttranslational modifications of ER, including the ER ubiquitin-dependent proteolysis. Overall, these findings suggest that the fetal brain might be less responsive to estrogens during late pregnancy in the rat, thereby minimizing the known harmful effects of high levels of circulating maternal estrogens.