HMGA1 protein over-expression is a frequent feature of epithelial ovarian carcinomas.
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.
Masciullo
Valeria
V
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Baldassarre
Gustavo
G
Pentimalli
Francesca
F
Berlingieri
Maria Teresa
MT
Boccia
Angelo
A
Chiappetta
Gennaro
G
Palazzo
Juan
J
Manfioletti
Guidalberto
G
Giancotti
Vincenzo
V
Viglietto
Giuseppe
G
Scambia
Giovanni
G
Fusco
Alfredo
A
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
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D016373:DNA, Antisense; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins; D025741:HMGA1a Protein