Kruppel-like factors KLF2 and 6 and Ki-67 are direct targets of zoledronic acid in MCF-7 cells. Ebert, R., Zeck, S., Meissner-Weigl, J., Klotz, B., Rachner, T. D., Benad, P., Klein-Hitpass, L., Rudert, M., Hofbauer, L. C., & Jakob, F. Bone, 50(3):723–732, March, 2012.
doi  abstract   bibtex   
Bisphosphonates (BP) are used for the treatment of osteoporosis and bone metastases due to breast and prostate cancer. Recent clinical studies indicated a benefit in survival and tumor relapse with the supportive treatment of breast cancer using zoledronic acid (ZA), thus stimulating the debate about its putative anti-tumor activity in vivo. MCF-7 breast cancer cells were treated for 3 h (pulse treatment) and 72 h (permanent treatment) with ZA, and apoptosis rates and cell viability, defined as ATP content, were determined after 72 h. Permanent and pulse stimulation with ZA inhibited the viability of MCF-7 cells, which could partly be rescued by atorvastatin (Ator) pre-treatment but not by geranylgeranyl pyrophosphate (GGPP) co-treatment. Microarray analysis of ZA treated MCF-7 cells identified genes of the mevalonate pathway as significantly upregulated, which was verified by qPCR. Additionally the putative tumor suppressors kruppel-like factor 2 and 6 (KLF2 and KLF6) were markedly upregulated, while the classical proliferation marker Ki-67 was clearly downregulated. The expression of all three genes was confirmed by qPCR on mRNA level and by immunocytochemistry or Western blot staining. Expression of target genes were also analyzed in other breast (MDA-MB-231, BT-20, ZR75-1, T47D) and prostate (LNCaP, PC3) cancer cell lines by qPCR. ZA responsiveness of KLF2, KLF6 and Ki-67 could be verified in PC3 and T47D cells, KLF6 responsiveness in LNCaP and KLF2 responsiveness in MDA-MB-231 and
@article{ebert_kruppel-like_2012,
	title = {Kruppel-like factors {KLF2} and 6 and {Ki}-67 are direct targets of zoledronic acid in {MCF}-7 cells.},
	volume = {50},
	copyright = {Copyright A(c) 2011. Published by Elsevier Inc.},
	doi = {10.1016/j.bone.2011.11.025},
	abstract = {Bisphosphonates (BP) are used for the treatment of osteoporosis and bone metastases due to breast and prostate cancer. Recent clinical studies indicated a benefit in survival and tumor relapse with the supportive treatment of breast cancer using zoledronic acid (ZA), thus stimulating the debate about its putative anti-tumor activity in vivo. MCF-7 breast cancer cells were treated for 3 h (pulse treatment) and 72 h (permanent treatment) with ZA, and apoptosis rates and cell viability, defined as ATP content, were determined after 72 h. Permanent and pulse stimulation with ZA inhibited the viability of MCF-7 cells, which could partly be rescued by atorvastatin (Ator) pre-treatment but not by geranylgeranyl  pyrophosphate (GGPP) co-treatment. Microarray analysis of ZA treated MCF-7 cells  identified genes of the mevalonate pathway as significantly upregulated, which was verified by qPCR. Additionally the putative tumor suppressors kruppel-like factor 2 and 6 (KLF2 and KLF6) were markedly upregulated, while the classical proliferation marker Ki-67 was clearly downregulated. The expression of all three genes was confirmed by qPCR on mRNA level and by immunocytochemistry or Western blot staining. Expression of target genes were also analyzed in other breast (MDA-MB-231, BT-20, ZR75-1, T47D) and prostate (LNCaP, PC3) cancer cell lines by  qPCR. ZA responsiveness of KLF2, KLF6 and Ki-67 could be verified in PC3 and T47D cells, KLF6 responsiveness in LNCaP and KLF2 responsiveness in MDA-MB-231 and},
	language = {eng},
	number = {3},
	journal = {Bone},
	author = {Ebert, Regina and Zeck, Sabine and Meissner-Weigl, Jutta and Klotz, Barbara and Rachner, Tilman D. and Benad, Peggy and Klein-Hitpass, Ludger and Rudert, Maximilian and Hofbauer, Lorenz C. and Jakob, Franz},
	month = mar,
	year = {2012},
	pmid = {22166808},
	keywords = {Apoptosis/drug effects, Breast Neoplasms/*metabolism/pathology, Breast/drug effects/metabolism, Cell Line, Tumor, Cell Survival/drug effects, Diphosphonates/*pharmacology, Female, Humans, Imidazoles/*pharmacology, Ki-67 Antigen/*metabolism, Kruppel-Like Transcription Factors/*metabolism, Proto-Oncogene Proteins/*metabolism},
	pages = {723--732},
}

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