PubMed · 5386045
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L A Medina, A Lucchini, H Aste, W Koch, J Alvarez. 1969. [Gastrointestinal polyps].. https://pubmed.ncbi.nlm.nih.gov/5386045/
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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.
To elucidate the role of calcitonin gene-related peptide (CGRP) in regulating pituitary function, we investigated the effects of CGRP and the related peptide adrenomedullin (AdM) on the secretion of growth hormone (GH) in vitro from human pituitary adenoma cells, rat pituitary tumor (GH3) cells, and normal rat pituitary cells. In 3 of 5 human somatotroph adenomas, GH secretion was stimulated by CGRP (1-100 nM). In one case of somatotroph adenoma, GH release was observed following the addition of 10 nM GHRH and 10 nM CGRP. The addition of CGRP or AdM (1 pM-10 nM) evoked GH secretion from GH3 cells with a bell-shaped distribution curve. CGRP (100 pM) caused the maximum increase of GH secretion (172+/-14 (mean+/-S.D.)% of control). The addition of CGRP8-37, an antagonist of CGRP type 1 receptors, inhibited the stimulatory effect of AdM but did not inhibit the effect of CGRP. The addition of CGRP and AdM evoked moderate GH secretion from normal rat pituitary cells. These results suggested that CGRP is a new GH secretagogue in human and rat pituitary tumor cells.
BACKGROUND: Rectal epithelial proliferation (REP) measurements are used as a biomarker of risk for colorectal neoplasia and response to chemoprevention. The authors evaluated REP in screenees with and without a history of adenoma and its association with demographic and adenoma characteristics, diet, and other lifestyle habits. METHODS: Long term lifestyle habits were evaluated and proliferation assessed by in vitro bromodeoxyuridine labeling of rectal biopsies in 223 screenees, 132 of whom had adenomas removed > 3 years previously. Analyses included the total population, screenees with a previous history of adenomas and adenoma free screenees separately, and a subgroup of 55 matched adenoma cases and controls. RESULTS: Crypt proliferation measurements were not elevated in screenees with a history of adenomas compared with adenoma free screenees (mean total labeling index [LI] of 4.8% and 4.9%, respectively). This was confirmed by the case-control analysis, in which the LI of the most superficial crypt compartment was lower in the adenoma cases (P=0.05). Moreover, their total LI correlated negatively with the number of adenomas removed previously (P < 0.01). Proliferation was more frequent in the most superficial crypt compartments of female adenoma free screenees than in female screenees with a history of adenomas (P=0.02), and in men age > 65 years compared with younger men (P=0.06). In the total population, negative Spearman rank correlations were found between total LI and long term dietary intake of calcium (correlation coefficient [r]=-0.15; P=0.02), LI of the two most superficial crypt compartments and intake of fiber (r=-0.18; P=0.01), water (r=-0.12; P=0.08), and carbohydrates (not significant). A positive correlation was found between LI of the most superficial crypt compartment and cigarette smoking (r=0.4; P=0.02). CONCLUSIONS: REP measurements did not discriminate between screenees with a history of adenomas and adenoma free screenees. Long-term lifestyle habits, gender, and age were associated with REP levels and need to be considered when evaluating human intervention studies.