title: PTHrP expression in human MDA-MB-231 breast cancer cells is critical for tumor growth and survival and osteoblast inhibition.
abstract: This study examined the effects of parathyroid hormone-related protein (PTHrP) derived from human MDA-MB-231 breast cancer cells on the tumor growth and osteoblast inhibition. Results revealed that knocking down PTHrP expression in the breast cancer cells strikingly inhibited the formation of subcutaneous tumors in nude mice. PTHrP knockdown dramatically decreased the levels of cyclins D1 and A1 proteins and arrested the cell cycle progression at the G1 stage. PTHrP knockdown led to the cleavage of Caspase 8 and induced apoptosis of the tumor cells. Interestingly, knocking down PTHrP increased the levels of Beclin1 and LC3-II and promoted the formation of autophagosomes. Knocking down PTHrP expression significantly reduced the abilities of the breast cancer cells to inhibit osteoblast differentiation and bone formation in vitro and in vivo. Finally, we found that PTHrP activated its own expression through an autocrine mechanism in MDA-MB-231 cells. Collectively, these studies suggest that targeting PTHrP expression in the tumor cells could be a potential therapeutic strategy for breast cancers, especially those with skeletal metastases.
authors: Department of Immunology, Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors: Lu
authors: L
authors: Zheng
authors: Ke
authors: K
authors: Zhu
authors: Hongli
authors: H
authors: Jiao
authors: Zhongfang
authors: Z
authors: Zhao
authors: Lixiao
authors: L
authors: Zhang
authors: Mo
authors: M
authors: Liu
authors: Weimin
authors: W
authors: Deng
authors: Di
authors: D
authors: Chen
authors: Zhi
authors: Z
authors: Yao
authors: Guozhi
authors: G
authors: Xiao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D019898:Autocrine Communication / Q000235:genetics / Q000502:physiology; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D053181:Caspase 8 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D056750:Cyclin A1 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D056750:Cyclin A1; D017931:DNA Primers; D044162:Parathyroid Hormone-Related Protein; D019938:Cyclin D1; D053181:Caspase 8
keywords: MDA-MB-231 cell; PTHrP; autophagy; osteoblast; osteoclast; osteolysis
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