PubMed · 7396802
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R M Naclerio. 1980. Pathologic quiz case 1.. https://pubmed.ncbi.nlm.nih.gov/7396802/
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The high mobility group As (HMGAs) belong to a family of nonhistone nuclear proteins that orchestrate the assembly of nucleoprotein complexes. Through a complex network of protein-DNA and protein-protein interaction, they play important roles in gene transcription, recombination, and chromatin structure. This protein family is involved, through different mechanisms, in both benign and malignant neoplasias. We have recently reported that transgenic mice carrying the Hmga1 or Hmga2 genes under transcriptional control of the cytomegalovirus promoter develop pituitary adenomas secreting prolactin and growth hormone. We have shown that the mechanism of the HMGA2-induced pituitary adenoma is based on the increased E2F1 activity. The expression profile of mouse normal pituitary glands and adenomas induced in HMGA transgenic mice revealed an increased expression of the ccnb2 gene, coding for the cyclin B2 protein, in the neoplastic tissues compared with the normal pituitary gland. Here, we show, by electrophoretic mobility shift assay and chromatin immunoprecipitation, a direct binding of HMGA proteins to the promoter of ccnb2 gene, whereas luciferase assays showed that HMGAs are able to up-regulate ccnb2 promoter activity. Finally, we report an increased CCNB2 expression in human pituitary adenomas of different histotypes that is directly correlated with HMGA1 and HMGA2 expression. Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis.
BACKGROUND: The need for colonoscopy in patients with adenomas 5 mm or less in diameter that are detected by sigmoidoscopy is controversial. METHODS: We prospectively determined the prevalence of proximal colonic neoplasms in asymptomatic patients at average risk for colorectal cancer, each of whose index lesion on screening fiberoptic sigmoidoscopy was a benign adenoma. Polyps found on sigmoidoscopy underwent biopsy, and colonoscopy was recommended to all patients with neoplastic polyps. Rectosigmoid adenomas were classified as diminutive (< or = 5 mm in diameter), small (6 to 10 mm in diameter), or large (> or = 11 mm in diameter). RESULTS: Of 3496 consecutive patients referred for sigmoidoscopy, 311 had neoplastic rectosigmoid polyps; 108 of these patients were excluded from the analysis because of a history of colonic neoplasia, symptoms, prior colonic evaluation, or incomplete follow-up data. The remaining 203 patients made up the study group, and all underwent colonoscopy. Neoplasms were found in the proximal colon in 40 of 137 patients (29 percent) with diminutive index polyps, 15 of 52 patients (29 percent) with small index polyps, and 8 of 14 patients (57 percent) with large index polyps. Advanced neoplasms (adenomas > or = 10 mm in diameter, adenomas with a villous component or moderate-to-severe dysplasia, carcinoma in situ, or frank carcinoma) were found in 8 patients (6 percent), 5 patients (10 percent), and 4 patients (29 percent), respectively. Two patients with diminutive index polyps had proximal carcinoma in situ, and two had proximal stage I carcinomas; one patient with a large index polyp had proximal stage III carcinoma. CONCLUSIONS: The substantial prevalence of proximal colonic neoplasms, including advanced lesions, in asymptomatic average-risk patients with rectosigmoid adenomas < or = 5 mm in diameter warrants colonoscopy in these patients.
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