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Int J Biol Sci. 2013 Aug 21;9(8):830-41. doi: 10.7150/ijbs.7039. eCollection 2013.

PTHrP expression in human MDA-MB-231 breast cancer cells is critical for tumor growth and survival and osteoblast inhibition.

Author information

1
Department of Immunology, Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.

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.

KEYWORDS:

MDA-MB-231 cell; PTHrP; autophagy; osteoblast; osteoclast; osteolysis

PMID:
23983616
PMCID:
PMC3753447
DOI:
10.7150/ijbs.7039
[Indexed for MEDLINE]
Free PMC Article

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