PubMed · 7036056
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A E Mehta, G Tolis, C Goodyer, R McInnes. 1981. Prolactin update.. https://pubmed.ncbi.nlm.nih.gov/7036056/
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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: High grade prostatic intraepithelial neoplasia (PIN) is associated with coincident prostate carcinoma, and has been considered to be a precursor of prostate carcinoma. Most studies on PIN have been performed on total prostatectomy or core needle biopsy specimens. Few reports deal with the occurrence of PIN in consecutive surgical resections, which is the objective of the current study. METHODS: A total of 1135 nonselected surgical specimens from the prostate, examined during 1974 and 1975, underwent blind review by 2 experienced pathologists. There were 79 core needle biopsies, 731 transurethral resections of the prostate and 325 transvesical prostatic enucleations. The kappa coefficient for interobserver reproducibility was 0.66 for PIN and 0.86 for carcinoma. RESULTS: Grade 1 PIN was found in 9%, Grade 2 PIN in 32%, and Grade 3 PIN in 20% of the total cases. Atypical adenomatous hyperplasia (AAH) was found in 11% and adenocarcinoma in 27% of the cases. Grade 3 PIN was associated with coincident adenocarcinoma in 39% of the cases. The prevalence of carcinoma for cases with Grade 1 and 2 PIN did not exceed that of those with Grade 0 PIN. PIN was most commonly found in association with small carcinomas. The mean age of the entire group of patients was 70.0 years, and was 69.4 years for patients with PIN without coincident carcinoma. Patients with PIN and coincident carcinoma had a mean age of 71.7 years, similar to all PIN grades, but patients with carcinoma without PIN had the highest mean age, 73.3 years. CONCLUSIONS: PIN is a common histologic finding in tissues from prostatic resections. In this study, Grade 3 PIN was strongly associated with coincident carcinoma, but lower grade PIN was not. There was no association between PIN and AAH. Patients with PIN did not appear to have a higher mean age than corresponding patients without PIN.
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