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Adenoviral Transduction of TESTIN Gene into Breast and Uterine Cancer Cell Lines Promotes Apoptosis and Tumor Reduction In vivo

¹ Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University; ² Fox Chase Cancer Center, Philadelphia, Pennsylvania; ³ Thomas Jefferson University Hospital, Philadephia, PA; and ⁴ Centro Interdipartimentale per la Ricerca sul Cancro, Dipartimento di Medicina Sperimentale e Diagnostica, Universita' degli Studi di Ferrara, Ferrara, Italy

Requests for reprints: Carlo M. Croce, Comprehensive Cancer Center, Ohio State University, Wiseman Hall, Room 445D, 400 West 12th Avenue, Columbus, OH 43210. E-mail: Carlo.Croce{at}osumc.edu.

Purpose: The human TESTIN (TES) gene is a putative tumor suppressor gene in the fragile chromosomal region FRA7G at 7q31.1/2 that was reported to be altered in leukemia and lymphoma cell lines. In this report, we investigated the effect of TES gene expression in vivo to evaluate a possible role of TES gene in human cancer.

Experimental Design: We have analyzed the expression of TES gene in a panel of 25 breast tumors and 17 cell lines of breast, colon, and uterine cancers. Furthermore, to evaluate the potential of TES gene therapy, we studied the effects of adenoviral TES transduction (Ad-TES) in cell lines with undetectable TES expression (T47D and MES-SA) as well as in MCF-7 cell line where TES expression is normal.

Results: Twenty-five percent of primary breast tumor samples as well as the breast cancer cell line T47D and the uterine sarcoma cell line MES-SA were negative or displayed low levels of TES. After TES restoration by Ad-TES transduction, T47D and MES-SA cell lines underwent apoptosis. Furthermore, TES expression significantly reduced the tumorigenic potential of both T47D and MES-SA in nude mice, whereas the untreated cells and Ad-GFP-infected cells showed tumor growth in vivo. The TES-positive cell line control (MCF-7) was not affected by TES expression and did not show a reduction of tumorigenicity in nude mice after infection with Ad-TES.

Conclusions: Ad-TES expression inhibit the growth of breast and uterine cancer cells lacking of TES expression through caspase-dependent and caspase-independent apoptosis, respectively, suggesting that Ad-TES infection should be explored as a therapeutic strategy.

Key Words: TES • adenovirus • breast cancer • uterine sarcoma

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