Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RET gene rearrangements, which generate chimeric RET/PTC oncogenes, are early events in the evolution of thyroid papillary carcinomas. Expression of RET/PTC oncogenes promotes neoplastic transformation of cultured thyroid cells and of thyroid glands in transgenic mice. Notwithstanding these oncogenic effects, we have found that the expression of two RET/PTC oncogenes (H4-RET and RFG-RET) induces apoptosis of rat thyroid PC CL 3 cells. Promotion of thyroid cell death depends on the kinase activity of RET/PTC and on the phosphorylation of a tyrosine residue (tyrosine 1062) that maps in the carboxy-terminus of the RET protein. Tyrosine 1062 is essential for RET/PTC-mediated activation of the Ras/ERK pathway. Inhibition of Ras/ERK by a dominant negative Ras or by the MEKI inhibitor, PD98059, obstructed RET/PTC-mediated apoptosis. We also show that signals transmitted by tyrosine 1062 mediate proapoptotic events like Bcl-2 down regulation and Bax upregulation, and that adoptive overexpression of Bcl-2 overcomes RET/PTC-induced apoptosis. Thus, gene rearrangements that generate RET/PTC oncogenes subvert RET function by converting it into a chronically active kinase that is constitutively phosphorylated on tyrosine 1062. In turn, Y1062 phosphorylation transmits not only mitogenic but also proapoptotic signals to thyroid cells.
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PMID:Ras-mediated apoptosis of PC CL 3 rat thyroid cells induced by RET/PTC oncogenes. 1252 93

Mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct has not yet been reported. Much more common than this is secondary involvement of the extrahepatic bile duct in cases of disseminated lymphoma. A 59-year-old man manifesting jaundice was referred to our hospital. PTC revealed an extrahepatic bile duct stenosis from the hilum to the lower part of the choledochus. On the operative specimen, we examined L26/CD20, Bcl-2, UCHL-1/CD45RO, cyclin D1 and p53. Histologically, follicular colonization, centrocyte-like cells and lymphoepithelial lesion was observed. Tumor cells were positive for L26/CD20 and Bcl-2 and were negative for intracytoplasmic immunoglobulins, UCHL-1/CD45RO, cyclin D1 and p53. Pathological diagnosis was mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct. The authors present herein the first case of mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct. It was very difficult to distinguish from hilar cholangiocarcinoma clinically. Only incomplete stenosis of the bile duct and 18-F fluoro-2-deoxyglucose positron emission tomography (FDG-PET) could suggest this unusual clinical entity.
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PMID:Mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct. 1581 35

The aim of this study was to gain better insight into molecular changes which reflect disturbances in the balance between proliferation and apoptosis during progression of thyroid malignancy from papillary microcarcinoma (PMC) via clinically manifest papillary carcinoma (PTC) to anaplastic carcinoma (ATC). The apoptosis related molecules (Bcl-2, Bax) and proliferation related marker (PCNA) were analysed immunohistochemically in 120 archival cases comprising PMC (n=34), PTC (n=52) and ATC (n=34). In addition, in situ apoptotic cell death was analysed by the TUNEL method. The average Bcl-2 staining score did not differ between PMC and PTC (p>0.05), but was significantly lower in ATC (p<0.05).The Bax score was higher in PTCs and ATCs than in PMCs (p<0.05). Due to these changes, the Bcl-2/Bax ratio showed a marked decrease from PMC to ATC (p<0.05), while proliferation activity increased significantly from PTC to ATC (p<0.05). Despite high Bax expression, the rate of apoptotic cell death was low in the investigated carcinomas, especially in ATC, i.e. the increase in proliferative activity was not counterbalanced with appropriate cell death. Differences were found in the expression of apoptotic molecules (Bcl-2 and Bax), their ratio (Bcl-2 /Bax) and in the rate of apoptotic cell death and proliferative activity between PMC, PTC and ATC, indicating that disturbances in the balance between apoptosis and proliferation, in favour of the latter, occur gradually during the progression of malignancy in thyroid tumours.
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PMID:Changes in the balance between proliferation and apoptosis during the progression of malignancy in thyroid tumours. 1968 79

Berberine, an important natural isoquinoline alkaloid from traditional Chinese medicine, is reported to exhibit multiple pharmacological properties, including anti-microbial, anti-diabetes, anti-obesity, anti-inflammatory and anti-carcinogenic activities. Although studies have shown that a wide range of carcinoma cells could be inhibited by berberine, few studies involved thyroid carcinoma. We therefore examined the effect of berberine on papillary thyroid carcinoma (PTC, the most common subtype) and anaplastic thyroid carcinoma (ATC, the most malignant and aggressive subtype). Three thyroid carcinoma cell lines with different aberrant genotypes and one normal thyroid cell line were selected, including C643 (ATC, with H-RAS mutation), OCUT1 (ATC, with BRAFV600E and PIK3CA mutations), TPC1 (PTC, with RET/PTC1 rearrangement) and Htori3 (normal). We found that berberine inhibited the proliferation of C643, OCUT1 and TPC1 thyroid carcinoma cells in a dose- and time-dependent manner (p<0.01, compared with the control), while normal human thyroid cells showed less sensitivity to the cytotoxicity of berberine. Berberine-induced significant mitochondrial apoptosis, G0/G1 cell cycle arrest and inhibitive migration in thyroid carcinoma cells were also observed (p<0.05 or p<0.01, compared with the control). Increased Bax/Bcl-2, cleaved Caspase 3, P21 and decreased Cyclin E1, CDK2 and Vimentin were verified by western blot. Additionally, berberine caused markedly decreased p-AKT1 expression and disturbances in classic ERK MAPK as well as P38 and JNK MAPK pathways in diverse thyroid carcinoma cells. Therefore, berberine could modulate PI3K-AKT and MAPK signaling pathways in thyroid carcinoma cells, which leads to mitochondrial apoptosis, G0/G1 cell cycle arrest and suppressive migration. Berberine may represent a promising chemotherapy for the treatment of thyroid carcinoma.
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PMID:Berberine could inhibit thyroid carcinoma cells by inducing mitochondrial apoptosis, G0/G1 cell cycle arrest and suppressing migration via PI3K-AKT and MAPK signaling pathways. 2893 Dec 15

The aim of this study was to gain better insight into molecular changes which reflect disturbances in the balance between proliferation and apoptosis during progression of thyroid malignancy from papillary microcarcinoma (PMC) via clinically manifest papillary carcinoma (PTC) to anaplastic carcinoma (ATC). The apoptosis related molecules (Bcl-2, Bax) and proliferation related marker (PCNA) were analysed immunohistochemically in 120 archival cases comprising PMC (n=34), PTC (n=52) and ATC (n=34). In addition, in situ apoptotic cell death was analysed by the TUNEL method. The average Bcl-2 staining score did not differ between PMC and PTC (p>0.05), but was significantly lower in ATC (p<0.05).The Bax score was higher in PTCs and ATCs than in PMCs (p<0.05). Due to these changes, the Bcl-2/Bax ratio showed a marked decrease from PMC to ATC (p<0.05), while proliferation activity increased significantly from PTC to ATC (p<0.05). Despite high Bax expression, the rate of apoptotic cell death was low in the investigated carcinomas, especially in ATC, i.e. the increase in proliferative activity was not counterbalanced with appropriate cell death. Differences were found in the expression of apoptotic molecules (Bcl-2 and Bax), their ratio (Bcl-2 /Bax) and in the rate of apoptotic cell death and proliferative activity between PMC, PTC and ATC, indicating that disturbances in the balance between apoptosis and proliferation, in favour of the latter, occur gradually during the progression of malignancy in thyroid tumours.
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PMID:Changes in the balance between proliferation and apoptosis during the progression of malignancy in thyroid tumours. 3025 74