title: A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy.
abstract: We investigated the mRNA expression levels of all six antiapoptotic Bcl-2 subfamily members in 68 human cancer cell lines using qPCR techniques and measured the ability of known Bcl-2 inhibitors to induce cell death in 36 of the studied tumor cell lines. Our study reveals that Mcl-1 represents the anti-apoptotic Bcl-2 subfamily member with the highest mRNA levels in the lung, prostate, breast, ovarian, renal, and glioma cancer cell lines. In leukemia/lymphoma and melanoma cancer cell lines, Bcl-2 and Bfl-1 had the highest levels of mRNA, respectively. The observed correlation between the cell killing properties of known Bcl-2 inhibitors and the relative mRNA expression levels of anti-apoptotic Bcl-2 proteins provide critical insights into apoptosis-based anticancer strategies that target Bcl-2 proteins. Our data may explain current challenges of selective Bcl-2 inhibitors in the clinic, given that severe expression of Bcl-2 seems to be limited to leukemia cell lines. Furthermore, our data suggest that in most cancer types a strategy targeted to Mcl-1 inhibition, or combination of Bfl-1 and Mcl-1 inhibition for melanoma, may prove to be more successful than therapies targeting only Bcl-2.
authors.affiliation: Sanford/Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Placzek
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.forename: S
authors.initials: S
authors.lastname: Kitada
authors.forename: D
authors.initials: D
authors.lastname: Zhai
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: M
authors.initials: M
authors.lastname: Pellecchia
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D005454:Fluorescence Polarization; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D054852:Small Molecule Libraries