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Carcinogenesis Advance Access published online on May 9, 2003
Carcinogenesis, doi:10.1093/carcin/bgg075
© 2003 by Oxford University Press
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© 2003 Oxford University Press

CANCER BIOLOGY

HMGA1 protein overexpression is a frequent feature of epithelial ovarian carcinomas

Valeria Masciullo 1, Gustavo Baldassarre 2, Francesca Pentimalli 2, Maria Teresa Berlingieri 2, Angelo Boccia 2, Gennaro Chiappetta 3, Juan Palazzo 1, Guidalberto Manfioletti 4, Vincenzo Giancotti 4, Giuseppe Viglietto 2, Giovanni Scambia 5, Alfredo Fusco 2*

1 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust street, Philadelphia, PA 19107, USA
2 Dipartimento di Biologia e Patologia Cellulare e "Molecolare c/o Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli Federico II", via Pansini, 5, 80131 Naples, Italy
3 Istituto Nazionale dei Tumori di Napoli, Fondazione Senatore Pascale, via M. Semmola, 80131 Naples, Italy
4 Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, Università degli Studi di Trieste, 34127 Trieste, Italy
5 Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del S. Cuore, L.go A. Gemelli 8, 00168 Rome, Italy

* Corresponding author. E-mail: afusco{at}napoli.com.

Received 9 December 2002 ; revised 16 April 2003 ; accepted 22 April 2003

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 overexpressed in several human malignant tumors.

In this study, HMGA1 protein expression was investigated by immunohistochemistry in a series of forty-four epithelial ovarian specimens which included 4 normal ovarian tissues, 29 primary invasive carcinomas, 1 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, while 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 overexpression 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.

HMGA1, chromatin, ovary, carcinoma, immunohistochemistry
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