title: Correlated expression of HMGA2 and PLAG1 in thyroid tumors, uterine leiomyomas and experimental models.
abstract: In pleomorphic adenomas of the salivary glands (PASG) recurrent chromosomal rearrangements affecting either 8q12 or 12q14∼15 lead to an overexpression of the genes of the genuine transcription factor PLAG1 or the architectural transcription factor HMGA2, respectively. Both genes are also affected by recurrent chromosomal rearrangements in benign adipocytic tumors as e. g. lipomas and lipoblastomas. Herein, we observed a strong correlation between the expression of HMGA2 and PLAG1 in 14 benign and 23 malignant thyroid tumors. To address the question if PLAG1 can be activated by HMGA2, the expression of both genes was quantified in 32 uterine leiomyomas 17 of which exhibited an overexpression of HMGA2. All leiomyomas with HMGA2 overexpression also revealed an activation of PLAG1 in the absence of detectable chromosome 8 abnormalities affecting the PLAG1 locus. To further investigate if the overexpression of PLAG1 is inducible by HMGA2 alone, HMGA2 was transiently overexpressed in MCF-7 cells. An increased PLAG1 expression was observed 24 and 48 h after transfection. Likewise, stimulation of HMGA2 by FGF1 in adipose tissue-derived stem cells led to a simultaneous increase of PLAG1 mRNA. Altogether, these data suggest that HMGA2 is an upstream activator of PLAG1. Accordingly, this may explain the formation of tumors as similar as lipomas and lipoblastomas resulting from an activation of either of both genes by chromosomal rearrangements.
authors: Center for Human Genetics, University of Bremen, Bremen, Germany.
authors: Markus
authors: M
authors: Klemke
authors: Center for Human Genetics, University of Bremen, Bremen, Germany.
authors: Marietta Henrike
authors: MH
authors: Müller
authors: Institute of Statistics, University of Bremen, Bremen, Germany.
authors: Werner
authors: W
authors: Wosniok
authors: Center for Human Genetics, University of Bremen, Bremen, Germany.
authors: Dominique Nadine
authors: DN
authors: Markowski
authors: Center for Human Genetics, University of Bremen, Bremen, Germany.
authors: Rolf
authors: R
authors: Nimzyk
authors: Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors: Burkhard Maria
authors: BM
authors: Helmke
authors: Center for Human Genetics, University of Bremen, Bremen, Germany ; Institute for Medical Genetics, University of Rostock, University Medicine, Rostock, Germany.
authors: Jörn
authors: J
authors: Bullerdiek
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; C104382:PLAG1 protein, human