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Carcinogenesis Advance Access originally published online on May 9, 2003
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Carcinogenesis, Vol. 24, No. 7, 1191-1198, July 2003
© 2003 Oxford University Press

CANCER BIOLOGY

HMGA1 protein over-expression is a frequent feature of epithelial ovarian carcinomas

Valeria Masciullo1, Gustavo Baldassarre2,6, Francesca Pentimalli2, Maria Teresa Berlingieri2, Angelo Boccia2, Gennaro Chiappetta3, Juan Palazzo1, Guidalberto Manfioletti4, Vincenzo Giancotti4, Giuseppe Viglietto2, Giovanni Scambia5 and Alfredo Fusco2,7

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, I-80131 Naples, Italy
3 Istituto Nazionale dei Tumori di Napoli, Fondazione Senatore Pascale, via M. Semmola, I-80131 Naples, Italy
4 Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, Universita' degli Studi di Trieste, I-34127 Trieste, Italy
5 Istituto di Clinica ostetrica e Ginecologica, Universita' Cattolica del S. Cuore, L.go A. Gemelli 8, I-00168 Rome, Italy

7 To whom correspondence should be addressed Email: afusco{at}napoli.com

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.


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