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Y Dong

Publications and source records attributed to Y Dong.

316 records · Page 18Linked to original sources
PubMed1986

Down-regulation of glucocorticoid receptor mRNA by glucocorticoid hormones and recognition by the receptor of a specific binding sequence within a receptor cDNA clone.

A cDNA clone for the rat glucocorticoid receptor (GR) was used to study mechanisms of GR mRNA regulation. Treatment of rat hepatoma culture cells with 0.5 microM dexamethasone caused a small, initial increase in the GR mRNA level after 6 hr as well as a 50% to 95% reduction of the GR mRNA level after 24 hr of incubation when studied by RNA blot hybridization. After 72 hr, the initial GR mRNA level was restored. The down-regulation of GR mRNA levels appears to be independent of protein synthesis, since it also was observed in the presence of cycloheximide. However, cycloheximide caused a 4-fold increase in intracellular levels of GR mRNA. Using an immunoprecipitation assay, we could demonstrate that the GR specifically interacts with a GR cDNA clone, which represents a 2.6-kilobase fragment of the 3' nontranslated region of the GR mRNA. Nuclease protection experiments indicate the presence of several internal GR-binding regions in the above fragment.

Animals↗
PubMedDate not supplied

The overexpression of cyclin-dependent kinase (CDK) 2 in laryngeal squamous cell carcinomas.

We examined the expression of CDK2 using immunohistochemistry in 102 cases of laryngeal squamous cell carcinomas (LSCCs). The results showed that a total of 63.73% (65/102) patients revealed a CDK2 overexpression pattern and the CDK2 overexpression was correlated significantly with the tumor site, tumor size and advanced stage. A positive correlation between the CDK2 expression and proliferative activity of tumor cells measured by proliferating cell nuclear antigen was found (r = 0.894, p < 0.0001). The Kaplan-Meier's analysis showed that shorter disease-free survival was significantly associated with tumor grade, tumor size, lymph node metastasis and advanced stage. Overall survival was significantly associated with tumor grade, tumor size, lymph node metastasis, advanced stage and CDK2 overexpression. When CDK2 and PCNA were combined, the patients with both CDK2 overexpression and PCNA overexpression had a poorer overall survival. We concluded that the CDK2 overexpression may be associated with the malignant biological behavior of LSCCs.

Biomarkers, Tumor↗
PubMedDate not supplied

Methylselenocysteine modulates proliferation and apoptosis biomarkers in premalignant lesions of the rat mammary gland.

In the rat mammary carcinogenesis model, premalignant lesions known as intraductal proliferations (IDPs) are detectable within a few weeks after carcinogen treatment. These early transformed colonies are the precursors for the eventual formation of carcinomas. Our past research indicated that methylselenocysteine added to the diet of rats reduced the development of IDPs of all sizes (the size of each IDP was estimated operationally by the number of 5-micron serial sections showing the same pathology). The appearance of an IDP lesion represents a balance between cell proliferation and cell death. The modulation of these two cellular events by methylselenocysteine was investigated. The abdominal-inguinal mammary gland was excised 6 weeks after MNU administration. Proliferation and apoptosis were evaluated by BrdU labeling and the TUNEL assay, respectively. The expression levels of several cell cycle and apoptosis regulatory proteins, including cyclin D1, cyclin A, p27, p16, bcl-2, box and bak, were also assessed. All of the above endpoints were quantified by immunohistochemistry in paraffin-embedded sections. The results showed that the magnitude of the response to methylselenocysteine intervention seemed to depend on the size of the IDP lesion. For the purpose of this study, the small and large lesions were classified as those containing < or = 30 or > 30 serial sections, respectively. With the small lesions, methylselenocysteine significantly inhibited BrdU labeling and the expression of cyclin D1 and cyclin A, but increased the expression of p27. Interesting, only p27 was upregulated in the larger IDP lesions, while BrdU labeling and the cyclins were not affected. It is possible that the transformed phenotype becomes less sensitive to selenium-mediated arrest of proliferation once it progresses to a more advanced pathological stage. In contrast, methylselenocysteine stimulated apoptosis (TUNEL assay) by 3 to 4 fold, and this increase was evident in both the small and large IDP lesions. Consistent with the induction of apoptosis, a reduced expression of bcl-2 was also observed in the methylselenocysteine group. In summary, our data suggest that exposure to methylselenocysteine blocks clonal expansion of premalignant lesions at an early stage. This is achieved by simultaneously modulating certain molecular pathways that are responsible for inhibiting cell proliferation and enhancing apoptosis.

Animals↗