title: MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.
abstract: The Map kinase Activating Death Domain containing protein (MADD) isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.
authors: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Andrea
authors: A
authors: Turner
authors: Liang-Cheng
authors: LC
authors: Li
authors: Tania
authors: T
authors: Pilli
authors: Lixia
authors: L
authors: Qian
authors: Elizabeth Louise
authors: EL
authors: Wiley
authors: Suman
authors: S
authors: Setty
authors: Konstantin
authors: K
authors: Christov
authors: Lakshmy
authors: L
authors: Ganesh
authors: Ajay V
authors: AV
authors: Maker
authors: Peifeng
authors: P
authors: Li
authors: Prasad
authors: P
authors: Kanteti
authors: Tapas K
authors: TK
authors: Das Gupta
authors: Bellur S
authors: BS
authors: Prabhakar
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000235:genetics; D053218:Receptors, Death Domain / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; C105852:MADD protein, human; D034741:RNA, Small Interfering; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; D004317:Doxorubicin