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Petrocca F , Iliopoulos D , Qin HYR , Nicoloso MS , Yendamuri S , Wojcik SE , Shimizu M , Di Leva G , Vecchione A , Trapasso F , Godwin AK , Negrini M , Calin GA , Croce CM
Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer
Cancer Research. 2006 Nov;66(21) :10287-10291
PMID: ISI:000241781600012   
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ARLTS1 is a tumor suppressor gene initially described as a low-penetrance cancer gene: a truncated Trp149Stop (MUT) polymorphism is associated with general familial cancer aggregation and, particularly, high-risk familial breast cancer. DNA hypermethvlation has been identified as a mechanism of ARLTS1 expression down-regulation in lung carcinomas and B-cell chronic lymphocytic leukemia. We found that, in the majority of ovarian carcinomas (61.5%) and in a significant proportion of ovarian and breast cancer cell lines (45%), ARLTS-1 is strongly down-regulated due to DNA methylation in its promoter region. After ARLTS1 restoration by adenoviral transduction, only the negative TOV-112 and the homozygously mutated (MUT) MCF7 cells, but not the OV-90 cells expressing a normal ARLTS1 product, underwent apoptosis and inhibition of cell growth. Furthermore, ARLTS1 reexpression significantly reduced the tumorigenic potential of TOV-112 in nude mice. On the contrary, the ARLTS1-MUT induced significantly lower levels of apoptosis in infected cells and reduced in vivo tumorigenesis only partially, supporting the hypothesis that Trp149Stop polymorphism is retained in the general population and predisposes to cancer because of a reduction, but not full loss, of normal ARLTS1 function.
ISI Document Delivery No.: 101ZY Times Cited: 0 Cited Reference Count: 15 Cited References: ABUDUGUPUR A, 2002, CELL DEATH DIFFER, V9, P158 BULLRICH F, 2001, CANCER RES, V61, P6640 CALIN GA, 2002, P NATL ACAD SCI USA, V99, P15524 CALIN GA, 2005, NEW ENGL J MED, V352, P1667 FABBRI M, 2005, P NATL ACAD SCI USA, V102, P15611 FRANK B, 2005, NEW ENGL J MED, V353, P313 FRANK B, 2006, INT J CANCER, V118, P2505 FRANK B, 2006, INT J CANCER, V119, P1736 JEMAL A, 2006, CA-CANCER J CLIN, V56, P106 MABUCHI H, 2001, CANCER RES, V61, P2870 MASOJC B, 2006, BREAST CANCER RES TR, V99, P59 NAROD SA, 2002, NAT REV CANCER, V2, P113 SELLICK GS, 2006, NEW ENGL J MED, V354, P1204 WENNERBERG K, 2005, J CELL SCI, V118, P843 ZAIDI AU, 2001, J NEUROPATH EXP NEUR, V60, P937