title: HMGA1 protein over-expression is a frequent feature of epithelial ovarian carcinomas.
abstract: High mobility group A 1 (HMGA1) proteins are chromatinic factors, which are absent or expressed at very low levels in normal adult tissues, while they are over-expressed in several human malignant tumors. In this study, HMGA1 protein expression was investigated by immunohistochemistry in a series of 44 epithelial ovarian specimens, which included four normal ovarian tissues, 29 primary invasive carcinomas, one metastatic ovarian tumor and 10 low malignant potential (LMP) tumors. HMGA1 staining was not detected in normal ovarian surface epithelium, which is the area from which ovarian adenocarcinoma frequently arises. HMGA1 proteins were expressed at low levels in some LMP tumors, whereas they were present in abundance in most of the primary ovarian adenocarcinomas. RT-PCR and western blot analysis correlated with immunohistochemical data. We demonstrated that the suppression of HMGA1 protein synthesis by an adenovirus carrying the HMGA1 gene in antisense orientation (Ad-Yas-GFP) inhibited the growth of two human ovarian carcinoma cell lines (OVCAR-5 and OVCAR-8). These results confirm HMGA1 over-expression as a general feature of human malignant neoplasias, including ovarian cancer and suggest that suppression of HMGA1 protein synthesis by an antisense adenoviral vector may represent a new and promising gene therapy for the treatment of ovarian cancer.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Masciullo
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baldassarre
authors.forename: Francesca
authors.initials: F
authors.lastname: Pentimalli
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Berlingieri
authors.forename: Angelo
authors.initials: A
authors.lastname: Boccia
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.forename: Juan
authors.initials: J
authors.lastname: Palazzo
authors.forename: Guidalberto
authors.initials: G
authors.lastname: Manfioletti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Giancotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viglietto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics*; D000256:Adenoviridae / Q000235:genetics; D017931:DNA Primers; D016373:DNA, Antisense / Q000235:genetics; D005260:Female; D051380:GRB2 Adaptor Protein; D015972:Gene Expression Regulation, Neoplastic; D025741:HMGA1a Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D010051:Ovarian Neoplasms / Q000235:genetics*; D011506:Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D016373:DNA, Antisense; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins; D025741:HMGA1a Protein