title: Id-1 regulates Bcl-2 and Bax expression through p53 and NF-kappaB in MCF-7 breast cancer cells.
abstract: Although increasing evidence supports the protective role of inhibitor of differentiation and DNA binding-1 (Id-1) against anticancer drug-induced apoptosis, the underlying molecular mechanisms seem to vary depending on the tumor system. Here, we examined the direct role of Id-1 in MCF-7 breast cancer cells by ectopically overexpressing Id-1 under serum-free condition, where the endogenous Id-1 expression was suppressed. Id-1 expression resulted in increased number of viable cells, reduced Bax expression, enhanced Bcl-2 expression, but no change in Bcl-xL expression. The expression of nuclear factor-kappaB (NF-kappaB) was augmented, while those of p53 and IkappaB were reduced. Such changes in p53 and NF-kappaB pathways were also functional, as assessed by real-time polymerase chain reactions and reporter assays of their known downstream targets, p21 and Il-6, as well as Bax and Bcl-2 genes. Finally, Id-1 played a protective role against taxol-induced apoptosis in breast cancer cells as assessed by MTT assay and apoptotic cell count upon taxol treatment (0-200 nM). Reduced Bax expression and enhanced Bcl-2 expression by Id-1 were also noted in the presence of taxol. Taken together, we present a molecular mechanism where Id-1 regulates p53 and NF-kappaB pathways, which in turn regulates Bax and Bcl-2 genes, thus providing a survival advantage under exogenous stress such as serum-free or taxol treatment in MCF-7 breast cancer cells. In this regard, inactivation of Id-1 may provide a potential therapeutic strategy leading to inhibition of breast cancer progression and anti-cancer drug resistance.
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seongdong-gu, Seoul, Republic of Korea.
authors.forename: Hwan
authors.initials: H
authors.lastname: Kim
authors.forename: Heekyoung
authors.initials: H
authors.lastname: Chung
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jeong-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Mi-Yun
authors.initials: MY
authors.lastname: Oh
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Kim
authors.forename: Gu
authors.initials: G
authors.lastname: Kong
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013347:Subcellular Fractions; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C497453:ID1 protein, human; D007211:Indoles; D051798:Inhibitor of Differentiation Protein 1; D015850:Interleukin-6; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C007293:DAPI; D017239:Paclitaxel