Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations of K-ras gene have been demonstrated in 40-50% of colorectal cancer and large adenoma (>1 cm). This study was intended to clarify the correlation between the existence of K-ras oncogene and the pathological features of colorectal adenomas using our recently developed membrane arrays. Moreover, the downstream genes regulated by K-ras oncogene were explored to serve as potential biomarkers in the early diagnosis and risk assessment of patients with colorectal adenoma. Specimens were collected from 70 patients with colorectal adenoma. The alterations of K-ras oncogene were analyzed by direct sequencing and our constructed membrane arrays, respectively. The results of direct sequencing showed that 21 of 70 samples (30%) had K-ras gene mutations. The most frequently mutated sites included codons 12, 13, 15 and 18. Furthermore, activated K-ras oncogene was identified in 18 of 70 (25.7%) adenoma by membrane arrays. Statistical analyses showed that the membrane array had the accuracy of 90.0%, sensitivity of 88.9%, and specificity of 90.4%. The frequency of the mutational sites of K-ras gene was located as follows: codon 12, 100% (4/4); codon 13, 100% (4/4); codon 15, 75% (6/8); and codon 18, 100% (2/2). The analysis of the correlation between the experimental data and pathological characteristics of adenoma showed that activated K-ras oncogenes were significantly associated with the size, number and histology of adenomas (all P<0.001). Finally, we found the downstream genes activated by K-ras oncogene, including B-cell CLL/lymphoma 2 (BCL2), Homo sapiens H2A histone family, member Z (H2AFZ), Homo sapiens RAP1B, member of RAS oncogene family (RAP1B), Homo sapiens T-box 19 (TBX19), Homo sapiens E2F transcription factor 4, p107/p130-binding (E2F4) and matrix metallopeptidase 1 (MMP1), of which were overexpressed in most of all examined adenomas. These genes were then suggested to have functions involved in cell growth. The preliminary results indicated that the accuracy of membrane arrays was comparable to conventional DNA sequencing in the detection of activated K-ras oncogenes. Therefore, we propose that activated K-ras oncogene in colorectal adenomas may play an important role in the subsequent colorectal carcinogenesis through a group of K-ras-related molecular targets.
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PMID:Molecular mechanisms underlying the tumorigenesis of colorectal adenomas: correlation to activated K-ras oncogene. 1708 45

The T-box 19 (TBX19) gene encodes a transcription factor characterized by a highly conserved DNA-binding motif (T-box). Recent studies have revealed that TBX19 has been identified as one of the genes activated by KRAS mutations, and is upregulated in colon adenoma. These results indicate that TBX19 may work as an oncogene in colorectal cancer (CRC). However, the expression and role of TBX19 have yet to be investigated. Here, we investigated TBX19 mRNA and protein expressions in colon cancer cells or surgically resected CRC. We found that TBX19 mRNA expression was significantly increased in tumorous tissues compared to that in non-tumorous tissues, and increased TBX19 mRNA expression was associated with positive lymph node metastasis in our cohort. The expression of TBX19 mRNA was not correlated with that of TBX19 protein in tissue sample taken from the CRC patients. Moreover, TBX19 showed positive staining even in the normal colonic tissues and the adjacent non-tumorous tissues. These results suggest that the expression of TBX19 protein is not correlated with the expression of TBX19 mRNA. In addition, our results promote further investigations into the impact of TBX19 upregulation on colorectal carcinogenesis, as well as the underlying mechanisms.
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PMID:TBX19 is overexpressed in colorectal cancer and associated with lymph node metastasis. 2919 61

Functioning (FCA) and silent corticotroph (SCA) pituitary adenomas act differently from a clinical perspective, despite both subtypes showing positive TBX19 (TPIT) and/or adrenocorticotropic hormone (ACTH) staining by immunohistochemistry. They are challenging to treat, the former due to functional ACTH production and consequently hypercortisolemia, and the latter due to invasive and recurrent behavior. Moreover, the molecular mechanisms behind their distinct behavior are not clear. We investigated global transcriptome and proteome changes in order to identify signaling pathways that can explain FCA and SCA differences (e.g., hormone production vs. aggressive growth). In the transcriptomic study, cluster analyses of differentially expressed genes revealed two distinct groups in accordance with clinical and histological classification. However, in the proteomic study, a greater degree of heterogeneity within the SCA group was found. Genes and proteins related to protein synthesis and vesicular transport were expressed by both adenoma groups, although different types and a distinct pattern of collagen/extracellular matrix proteins were presented by each group. Moreover, several genes related to endoplasmic reticulum protein processing were overexpressed in the FCA group. Together, our findings shed light on the different repertoires of activated signaling pathways in corticotroph adenomas, namely, the increased protein processing capacity of FCA and a specific pattern of adhesion molecules that may play a role in the aggressiveness of SCA.
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PMID:Distinct Pattern of Endoplasmic Reticulum Protein Processing and Extracellular Matrix Proteins in Functioning and Silent Corticotroph Pituitary Adenomas. 3306 52