TY - JOUR
T1 - Tumor suppressor functions of ARLTS1 in lung cancers
AU - Yendamuri, Sai
AU - Trapasso, Francesco
AU - Ferracin, Manuela
AU - Cesari, Rossano
AU - Sevignani, Cinzia
AU - Shimizu, Masayoshi
AU - Rattan, Shashi
AU - Kuroki, Tamotsu
AU - Dumon, Kristoffel R.
AU - Bullrich, Florencia
AU - Liu, Chang Gong
AU - Negrini, Massimo
AU - Williams, Noel N.
AU - Kaiser, Larry R.
AU - Croce, Carlo M.
AU - Calin, George A.
PY - 2007/8/15
Y1 - 2007/8/15
N2 - ARLTS1 is a newly characterized tumor suppressor gene located at chromosome 13q14.3 and involved in the pathogenesis of various types of tumors: two single-nucleotide polymorphisms, one of them responsible for protein truncation, were found statistically associated with familial malignancies, whereas DNA hypermethylation and genomic deletions have been identified as a mechanism of ARLTS1 down-regulation in sporadic cancers. We found that in a large portion of lung carcinomas (37%) and in all analyzed lung cancer cell lines, ARLTS1 is strongly down-regulated due to DNA methylation in its promoter region. After its restoration by adenoviral transduction, ARLTS1-negative A549 and H1299 cells underwent apoptosis and inhibition of cell growth. Furthermore, ARLTS1 reexpression significantly reduced the ability of A549 and H1299 to form tumors in nude mice. Finally, we identified ∼650 transcripts differentially expressed after restoration of ARLTS1 expression in A549 cells, suggesting that various pathways involved in cell survival, proliferation, signaling, and development mediate the effects of wild-type ARLTS1 in a lung cancer system.
AB - ARLTS1 is a newly characterized tumor suppressor gene located at chromosome 13q14.3 and involved in the pathogenesis of various types of tumors: two single-nucleotide polymorphisms, one of them responsible for protein truncation, were found statistically associated with familial malignancies, whereas DNA hypermethylation and genomic deletions have been identified as a mechanism of ARLTS1 down-regulation in sporadic cancers. We found that in a large portion of lung carcinomas (37%) and in all analyzed lung cancer cell lines, ARLTS1 is strongly down-regulated due to DNA methylation in its promoter region. After its restoration by adenoviral transduction, ARLTS1-negative A549 and H1299 cells underwent apoptosis and inhibition of cell growth. Furthermore, ARLTS1 reexpression significantly reduced the ability of A549 and H1299 to form tumors in nude mice. Finally, we identified ∼650 transcripts differentially expressed after restoration of ARLTS1 expression in A549 cells, suggesting that various pathways involved in cell survival, proliferation, signaling, and development mediate the effects of wild-type ARLTS1 in a lung cancer system.
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U2 - 10.1158/0008-5472.CAN-07-1481
DO - 10.1158/0008-5472.CAN-07-1481
M3 - Article
C2 - 17699778
AN - SCOPUS:34548049246
SN - 0008-5472
VL - 67
SP - 7738
EP - 7745
JO - Cancer Research
JF - Cancer Research
IS - 16
ER -