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Journal of Environmental Pathology, Toxicology and Oncology
Facteur d'impact: 1.241 Facteur d'impact sur 5 ans: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Imprimer: 0731-8898
ISSN En ligne: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2015013472
pages 213-225

Role of GLI1 and NDRG1 in Increased Resistance to Apoptosis Induction

Feng Wu
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York
William N. Rom
Division of Pulmonary and Critical Care Medicine, and Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Minori Koshiji
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York; Clinical Oncology, Merck & Co., Inc., Whitehouse Station, New Jersey
Yiqun Mo
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York; Department of Environmental and Occupational Health Sciences, University of Louisville, Louisville, Kentucky
Yukio Hosomi
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York; Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
Kam-Meng Tchou-Wong
Division of Pulmonary and Critical Care Medicine, and Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA

RÉSUMÉ

We examined the effects of GLI1 expression in PW mouse embryo fibroblasts and H441 lung carcinoma cells. Ectopic expression of GLI1 in PW cells induced anchorage-independent growth and increased resistance to staurosporine-induced apoptosis, and overexpression of GLI1 in H441 cells caused resistance to apoptosis induced by staurosporine and etoposide. GLI1 expression in both H441 and PW cells was associated with increased expression of NDRG1, a gene known to be downregulated by the MYC family of proteins, indicating that upregulation of NDRG1 by GLI1 is not cell-type specific. Consistent with suppression of NDRG1 by c-MYC and N-MYC, increased NDRG1 expression correlated with decreased expression of c-MYC and N-MYC in GLI1-expressing H441 and GLI1-expressing PW cells, respectively. Downregulation of GLI1 expression in A549 cells by siRNA transfection increased sensitivity to etoposide-induced apoptosis, and downregulation of NDRG1 expression in H441 cells by siRNA transfection increased sensitivity to etoposide-induced apoptosis. Of clinical significance, inhibition of GLI1 and NDRG1 expression may increase sensitivity of cancer cells to chemotherapeutic drugs. Strategies that aim to inhibit GLI1 function and NDRG1 expression may be useful for targeted therapy of cancers induced by the SHH-GLI signaling pathway.


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