Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer

Fabio Petrocca, Dimitrios Iliopoulos, Haiyan R. Qin, Milena S. Nicoloso, Say Yendamuri, Sylwia E. Wojcik, Masayoshi Shimizu, Gianpiero Di Leva, Andrea Vecchione, Francesco Trapasso, Andrew K. Godwin, Massimo Negrini, George A. Calin, Carlo M. Croce

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

ASLTS1 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 hypermethylation 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%), ARLTS1 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 AKLTS1 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.

Original languageEnglish
Pages (from-to)10287-10291
Number of pages5
JournalCancer Research
Volume66
Issue number21
DOIs
Publication statusPublished - Nov 1 2006

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Tumor Suppressor Genes
Ovarian Neoplasms
Apoptosis
Carcinoma
Penetrance
Neoplasm Genes
MCF-7 Cells
DNA Methylation
B-Cell Chronic Lymphocytic Leukemia
Genetic Promoter Regions
Nude Mice
Neoplasms
Carcinogenesis
Down-Regulation
Breast Neoplasms
Cell Line
Lung
DNA
Growth
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Petrocca, F., Iliopoulos, D., Qin, H. R., Nicoloso, M. S., Yendamuri, S., Wojcik, S. E., ... Croce, C. M. (2006). Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer. Cancer Research, 66(21), 10287-10291. https://doi.org/10.1158/0008-5472.CAN-06-2289

Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer. / Petrocca, Fabio; Iliopoulos, Dimitrios; Qin, Haiyan R.; Nicoloso, Milena S.; Yendamuri, Say; Wojcik, Sylwia E.; Shimizu, Masayoshi; Di Leva, Gianpiero; Vecchione, Andrea; Trapasso, Francesco; Godwin, Andrew K.; Negrini, Massimo; Calin, George A.; Croce, Carlo M.

In: Cancer Research, Vol. 66, No. 21, 01.11.2006, p. 10287-10291.

Research output: Contribution to journalArticle

Petrocca, F, Iliopoulos, D, Qin, HR, Nicoloso, MS, Yendamuri, S, Wojcik, SE, Shimizu, M, Di Leva, G, Vecchione, A, Trapasso, F, Godwin, AK, Negrini, M, Calin, GA & Croce, CM 2006, 'Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer', Cancer Research, vol. 66, no. 21, pp. 10287-10291. https://doi.org/10.1158/0008-5472.CAN-06-2289
Petrocca F, Iliopoulos D, Qin HR, Nicoloso MS, Yendamuri S, Wojcik SE et al. Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer. Cancer Research. 2006 Nov 1;66(21):10287-10291. https://doi.org/10.1158/0008-5472.CAN-06-2289
Petrocca, Fabio ; Iliopoulos, Dimitrios ; Qin, Haiyan R. ; Nicoloso, Milena S. ; Yendamuri, Say ; Wojcik, Sylwia E. ; Shimizu, Masayoshi ; Di Leva, Gianpiero ; Vecchione, Andrea ; Trapasso, Francesco ; Godwin, Andrew K. ; Negrini, Massimo ; Calin, George A. ; Croce, Carlo M. / Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer. In: Cancer Research. 2006 ; Vol. 66, No. 21. pp. 10287-10291.
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