Adenoviral transduction of TESTIN gene into breast and uterine cancer cell lines promotes apoptosis and tumor reduction in vivo.
OBJECTIVE
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.


METHODS
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.
Sarti
Manuela
M
Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA.
Sevignani
Cinzia
C
Calin
George A
GA
Aqeilan
Rami
R
Shimizu
Masayoshi
M
Pentimalli
Francesca
F
Picchio
Maria Cristina
MC
Godwin
Andrew
A
Rosenberg
Anne
A
Drusco
Alessandra
A
Negrini
Massimo
M
Croce
Carlo M
CM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D020169:Caspases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D003598:Cytoskeletal Proteins; D005260:Female; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins / Q000627:therapeutic use*; D006801:Humans; D060588:LIM Domain Proteins; D051379:Mice; D008819:Mice, Nude; D016601:RNA-Binding Proteins; D012513:Sarcoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000627:therapeutic use*; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D016601:RNA-Binding Proteins; C429688:TES protein, human; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D020169:Caspases