The expression pattern of the Hmgic gene during development

Hirning‐Folz, Ulrike; Wilda, Monika; Rippe, Volkhard; Bullerdiek, Jörn; Hameister, Horst

doi:10.1002/(sici)1098-2264(199812)23:4<350::aid-gcc10>3.3.co;2-5

Cited by 45 publications

(56 citation statements)

References 15 publications

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“…High-mobility group A2 expression has been shown to be undetectable or to remain at low levels in normal adult tissues (Manfioletti et al, 1991;Zhou et al, 1995;Rogalla et al, 1996;Rommel et al, 1997;Hirning-Folz et al, 1998;Gattas et al, 1999). In the present study, however, a highly sensitive RT -PCR analysis revealed the expression of the HMGA2 gene in non-neoplastic pancreatic tissue, although its expression level was significantly lower than that in carcinoma.…”

Section: Discussioncontrasting

confidence: 52%

“…High-mobility group A2 has been shown to be expressed abundantly during embryogenesis, but its expression is either undetectable or remains at low levels in other normal adult tissues (Manfioletti et al, 1991;Zhou et al, 1995;Rogalla et al, 1996;Rommel et al, 1997;Hirning-Folz et al, 1998), suggesting that HMGA2 plays an important role (or roles) in cell proliferation and/ or differentiation. Consistent with this, it has been demonstrated that HMGA proteins are phosphorylated in a cell-cycle-dependent manner (Reeves et al, 1991).…”

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An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue

et al. 2003

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The altered form of the high-mobility group A2 (HMGA2) gene is somehow related to the generation of human benign and malignant tumours of mesenchymal origin. However, only a few data on the expression of HMGA2 in malignant tumour originating from epithelial tissue are available. In this study, we examined the HMGA2 expression level in pancreatic carcinoma, and investigated whether alterations in the HMGA2 expression level are associated with a malignant phenotype in pancreatic tissue. High-mobility group A2 mRNA and protein expression was determined in eight surgically resected specimens of non-neoplastic tissue (six specimens of normal pancreatic tissue and two of chronic pancreatitis tissue) and 27 pancreatic carcinomas by highly sensitive reverse transcriptase -polymerase chain reaction (RT -PCR) techniques and immunohistochemical staining, respectively. Reverse transcriptase -polymerase chain reaction analysis revealed the expression of the HMGA2 gene in non-neoplastic pancreatic tissue, although its expression level was significantly lower than that in carcinoma. Immunohistochemical analysis indicated that the presence of the HMGA2 gene in non-neoplastic pancreatic tissue observed in RT -PCR reflects its abundant expression in islet cells, together with its focal expression in duct epithelial cells. Intense and multifocal or diffuse HMGA2 immunoreactivity was noted in all the pancreatic carcinoma examined. A strong correlation between HMGA2 overexpression and the diagnosis of carcinoma was statistically verified. Based on these findings, we propose that an increased expression level of the HMGA2 protein is closely associated with the malignant phenotype in the pancreatic exocrine system, and accordingly, HMGA2 could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignant cells from non-neoplastic pancreatic exocrine cells.

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Section: Discussioncontrasting

confidence: 52%

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An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue

et al. 2003

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“…10). Like IMP2, HMGA2 is an oncofetal protein: it is expressed at high levels during embryonic development (11,12), whereas it is hardly detectable in adult tissues (13). In many tumor types, the HMGA2 gene is disrupted or aberrantly expressed, making this gene probably the most frequently rearranged gene in human neoplasias (reviewed in refs.…”

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confidence: 99%

HMGA2 Regulates Transcription of the Imp2 Gene via an Intronic Regulatory Element in Cooperation with Nuclear Factor-κB

Cleynen

Brants

Peeters

et al. 2007

Molecular Cancer Research

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IMP2 (insulin-like growth factor-II mRNA binding protein 2) is an oncofetal protein that is aberrantly expressed in several types of cancer. We recently identified the Imp2 gene as a target gene of the architectural transcription factor HMGA2 (high mobility group A2) and its tumor-specific truncated form HMGA2Tr. In this study, we investigated the mechanism via which HMGA2 regulates Imp2 gene expression. We show that HMGA2 and HMGA2Tr directly regulate transcription of the Imp2 gene by binding to an AT-rich regulatory region located in the first intron.In reporter experiments, we show that this AT-rich regulatory region mimics the response of the endogenous Imp2 gene to HMGA2 and HMGA2Tr. Furthermore, we show that a consensus nuclear factor-KB (NF-KB) binding site located immediately adjacent to the AT-rich regulatory region binds NF-KB and that NF-KB and HMGA2 cooperate to regulate Imp2 gene expression. Finally, we provide evidence that there is a strong and statistically significant correlation between HMGA2 and IMP2 gene expression in human liposarcomas.

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“…HMGI-C and HMGI(Y) are members of the HMGI family of "highmobility group" (HMG) proteins. They act as architectural transcription factors and are commonly expressed in embryonal cells Hirning-Folz et al, 1998), in transformed cells with a malignant phenotype Bussemakers et al, 1991;Giancotti et al, 1987;1989;Ram et al, 1993), and in a variety of human cancers (Bandiera et al, 1998;Chiappetta et al, 1995;1998;Fedele et al, 1996;Rogalla et al, 1997;Rommel et al, 1997;Tamimi et al, 1993). HMGI-C and HMGI(Y) genes are located at 12q15 and 6p21 (Friedmann et al, 1993), respectively.…”

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HMGI-C and HMGI(Y) Immunoreactivity Correlates with Cytogenetic Abnormalities in Lipomas, Pulmonary Chondroid Hamartomas, Endometrial Polyps, and Uterine Leiomyomas and is Compatible with Rearrangement of the HMGI-C and HMGI(Y) Genes

Tallini

Vanni

Manfioletti

et al. 2000

Laboratory Investigation

134

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SUMMARY:High-mobility group (HMG) proteins are nonhistone nuclear proteins that play an important role in the regulation of chromatin structure and function. HMGI-C and HMGI(Y) are members of the HMGI family of HMG proteins, and their expression in adult tissues generally correlates with malignant tumor phenotypes. However, HMGI-C and HMGI(Y) dysregulation as a result of specific rearrangements involving 12q15 and 6p21, the respective chromosomal sites in which the HMGI-C and HMGI(Y) genes are located, is also identified in a variety of common benign mesenchymal tumors, such as lipomas and uterine leiomyomata. The general prevalence of HMGI-C and HMGI(Y) protein expression and its correlation with chromosomal alterations in these benign tumors are unknown. We analyzed 95 human tumors (20 lipomas, 21 pulmonary chondroid hamartomas, 26 uterine leiomyomata, and 28 endometrial polyps) representing a selection of the benign lesions in which karyotypic alterations involving the chromosomal regions 12q15 and 6p21 are frequently detected. All cases were successfully karyotyped and some of them analyzed by fluorescent in situ hybridization with probes spanning the HMGI-C and HMGI(Y) genes. The results of this study demonstrate that expression of HMGI-C or HMGI(Y) is a common occurrence in lipomas, pulmonary chondroid hamartomas, leiomyomata, and endometrial polyps; that it correlates with 12q15 and 6p21 chromosomal alterations (p Ͻ 0.001); and that it is compatible with rearrangement of the HMGI-C and HMGI(Y) genes. The expression pattern and cellular localization of the immunoreactivity support the view that in biphasic lesions composed of a mixture of both stromal and epithelial cells, such as pulmonary chondroid hamartoma and endometrial polyps, the mesenchymal component is the site of the HMGI genetic alterations. (Lab Invest 2000, 80:359-369).

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The expression pattern of the Hmgic gene during development

Cited by 45 publications

References 15 publications

An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue

An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue

HMGA2 Regulates Transcription of the Imp2 Gene via an Intronic Regulatory Element in Cooperation with Nuclear Factor-κB

HMGI-C and HMGI(Y) Immunoreactivity Correlates with Cytogenetic Abnormalities in Lipomas, Pulmonary Chondroid Hamartomas, Endometrial Polyps, and Uterine Leiomyomas and is Compatible with Rearrangement of the HMGI-C and HMGI(Y) Genes

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