HMGI(Y) gene expression as a potential marker of thyroid follicular carcinoma

Czyz, W; Balcerczak, Ewa; Jakubiak, Magdalena; Pasieka, Zbigniew; Kuzdak, Krzysztof; Mirowski, Marek

doi:10.1007/s00423-004-0479-6

Cited by 21 publications

(23 citation statements)

References 19 publications

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“…Other studies suggested the expression of HMGA1 as a suitable genetic marker to distinguish benign from malignant thyroid tumors (Chiappetta et al, 1995(Chiappetta et al, , 1998Berlingieri et al, 2002;Czyz et al, 2004). As for the RT-PCR analyses, one main disadvantage of HMGA1 is the existence of several retropseudogenes, which can lead to false-positive results in quantification experiments when RNA extractions are contaminated with genomic DNA.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of HMGA2 in thyroid carcinomas: A novel molecular marker to distinguish between benign and malignant follicular neoplasias

Belge

Meyer

Klemke

et al. 2007

Genes Chromosomes & Cancer

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The identification of molecular markers allowing to differentiate between benign and malignant thyroid tumors remains a diagnostic challenge. Herein, we have used the expression of the high mobility group protein gene HMGA2 and its protein, respectively, as a possible marker detecting malignant growth of thyroid tumors. HMGA2 belongs to the high mobility group proteins, i.e. small, highly charged DNA-binding proteins. While HMGA2 is highly expressed in most embryonic tissues, its expression in adult tissues is very low. However, a reactivation of HMGA2 expression has been described for various malignant tumors and often correlates with the aggressiveness of the tumors. The aim of this study was to investigate whether the HMGA2 expression can be used to detect malignant thyroid tumors. RNA from 64 formalin-fixed paraffin-embedded thyroid tissues including normal tissue (n 5 3), thyroiditis (n 5 2), and follicular adenomas (n 5 19) as well as follicular (n 5 9), papillary (n 5 28), and anaplastic (n 5 3) carcinomas was reverse transcribed. Finally, real-time quantitative RT-PCR was performed. Expression differences of up to 400-fold were detected between benign and malignant thyroid tumors. Based on HMGA2 expression alone, it was possible to distinguish between benign and malignant thyroid tissues with a sensitivity of 95.9% and a specificity of 93.9%. There was a highly significant (P < 0.001) difference with histology of the tumors being the gold standard between the benign lesions and malignant tumors. Our results show that even as a stand-alone marker HMGA2 expression has a high potential to improve diagnoses of follicular neoplasms of the thyroid. V V C 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Upregulation of HMGA2 in thyroid carcinomas: A novel molecular marker to distinguish between benign and malignant follicular neoplasias

Belge

Meyer

Klemke

et al. 2007

Genes Chromosomes & Cancer

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“…Many immediate- and delayed-early genes are required by cells to traverse the G1/S boundary of the cell cycle and function as oncogenes when aberrantly expressed. Further studies uncovered high levels of HMGA1 expression at the mRNA or protein level in human cancer cells or primary tumors from diverse tissues, including thyroid [45–48], lung [49–51], breast [52–59, 117], bladder [58], prostate [60–62], colon [63–68], pancreas [69–74], uterine corpus [75], uterine cervix [76], kidney [77], head and neck [78], nervous system [58, 79–84], stomach [85, 86], liver [87], and hematopoietic system [88–93, 118, 119]. HMGA1 expression is low or undetectable in normal tissue counterparts.…”

Section: Hmga1 Is Up-regulated In Rapidly Proliferating Cells and Camentioning

confidence: 99%

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development

Sumter¹,

Xian²,

Huso³

et al. 2016

CMM

103

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Background & Objectives Chromatin structure is the single most important feature that distinguishes a cancer cell from a normal cell histologically. Chromatin remodeling proteins regulate chromatin structure and high mobility group A (HMGA1) proteins are among the most abundant, nonhistone chromatin remodeling proteins found in cancer cells. These proteins include HMGA1a/HMGA1b isoforms, which result from alternatively spliced mRNA. The HMGA1 gene is overexpressed in cancer and high levels portend a poor prognosis in diverse tumors. HMGA1 is also highly expressed during embryogenesis and postnatally in adult stem cells. Overexpression of HMGA1 drives neoplastic transformation in cultured cells, while inhibiting HMGA1 blocks oncogenic and cancer stem cell properties. Hmga1 transgenic mice succumb to aggressive tumors, demonstrating that dysregulated expression of HMGA1 causes cancer in vivo. HMGA1 is also required for reprogramming somatic cells into induced pluripotent stem cells. HMGA1 proteins function as ancillary transcription factors that bend chromatin and recruit other transcription factors to DNA. They induce oncogenic transformation by activating or repressing specific genes involved in this process and an HMGA1 “transcriptome” is emerging. Although prior studies reveal potent oncogenic properties of HMGA1, we are only beginning to understand the molecular mechanisms through which HMGA1 functions. In this review, we summarize the list of putative downstream transcriptional targets regulated by HMGA1. We also briefly discuss studies linking HMGA1 to Alzheimer’s disease and type-2 diabetes. Conclusion Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and possibly for other diseases associated with aberrant HMGA1 expression.

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“…They form stereo-specific, multiprotein complexes termed “enhanceosomes” on the promoter/enhancer regions of genes, where they bind to the minor groove of AT-rich DNA sequences 3,5. HMGA1 proteins are overexpressed in a range of human cancers 6–9. By using a small sample of tumor tissues, Abe and colleagues previously demonstrated that HMGA1 is overexpressed in pancreatic cancers, although the clinical relevance of HMGA1 expression in this tumor type remains uncertain 10.…”

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High mobility group AT‐hook 1 (HMGA1) is an independent prognostic factor and novel therapeutic target in pancreatic adenocarcinoma

Liau

Rocha

Matros

et al. 2008

Cancer

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BACKGROUND. High mobility group AT‐hook 1 (HMGA1) proteins are architectural transcription factors that are overexpressed by pancreatic adenocarcinomas. The authors hypothesized that tumor HMGA1 status represents a novel prognostic marker in pancreatic adenocarcinoma. They also tested the hypothesis that HMGA1 promotes anchorage‐independent cellular proliferation and in vivo tumorigenicity. METHODS. Tumor HMGA1 expression was examined by immunohistochemical analysis of tissues from 89 consecutive patients who underwent resection for pancreatic adenocarcinoma. Short‐hairpin RNA (shRNA)‐mediated RNA interference was used to silence HMGA1 expression in MiaPaCa2 and PANC1 pancreatic cancer cells. Anchorage‐independent proliferation was assessed by using soft agar assays. The roles of phosphatidylinositol 3‐kinase (PI3‐K)/Akt and extracellular signal‐regulated kinase (ERK) signaling were investigated by using specific inhibitors and adenoviral dominant‐negative/active Akt constructs. In vivo tumorigenicity was assessed by using a nude mouse xenograft model. RESULTS. Tumor HMGA1 expression was detected in 93% of patients with pancreatic adenocarcinoma. Patients with HMGA1‐negative tumors had a significantly longer median survival than patients with HMGA1‐expressing cancers in univariate analysis (P = .0028) and in multivariate analysis (P<.05). shRNA‐mediated HMGA1 silencing resulted in significant reductions in anchorage‐independent proliferation in soft agar. Forced HMGA1 overexpression promoted proliferation in soft agar through a process that was dependent on PI3‐K/Akt‐activited signaling, but not on mitogen‐activated protein kinase (MEK)/ERK signaling. Targeted silencing of HMGA1 reduced tumor growth in vivo through reduced proliferation (Ki‐67 index) and increased apoptosis (terminal deoxynucleotidyl transferase nick‐end labeling). CONCLUSIONS. The current findings suggested that HMGA1 is an independent predictor of poor postoperative survival in patients with pancreatic adenocarcinoma. Furthermore, HMGA1 promotes tumorigenicity through a PI3‐K/Akt‐dependent mechanism. HMGA1 warrants further evaluation as a prognostic marker and therapeutic target in pancreatic cancer. Cancer 2008. © 2008 American Cancer Society.

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HMGI(Y) gene expression as a potential marker of thyroid follicular carcinoma

Abstract: On the basis of our study, we conclude that HMGI(Y) gene expression analysis could be helpful in differentiation between follicular carcinoma and adenoma.

Cited by 21 publications

References 19 publications

Upregulation of HMGA2 in thyroid carcinomas: A novel molecular marker to distinguish between benign and malignant follicular neoplasias

Upregulation of HMGA2 in thyroid carcinomas: A novel molecular marker to distinguish between benign and malignant follicular neoplasias

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development

High mobility group AT‐hook 1 (HMGA1) is an independent prognostic factor and novel therapeutic target in pancreatic adenocarcinoma

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