The effects of Hsp90 expression alteration on spinal metastases of breast carcinoma

Tumour Biol. 2013 Jun;34(3):1391-7. doi: 10.1007/s13277-012-0584-z. Epub 2013 Mar 1.

Abstract

Previous studies have demonstrated that Hsp90 is closely associated with tumor metastases, and inhibition of Hsp90 expression can result in reduced tumor invasiveness and migration capability. However, its role in spinal metastases of breast carcinoma remains unknown. The paper aimed to further detect Hsp90 expression in a mouse model of spinal metastases of breast carcinoma which was established by left ventricular injection of breast cancer cell lines TM40D to nude mice. The BALB/c nude mice were divided into four groups at random: blank control group (n=10), model group (n=30), negative control group (n=10), and experimental group (n=30). Mice in the experimental group were given intraperitoneal injection of 12 mg/kg 17-allylamino-demethoxy geldanamycin (17-AAG), an inhibitor for Hsp90. The protein and mRNA expressions of Hsp90 were respectively determined using immunohistochemistry and real-time PCR. Bioluminescence imaging, dissection, and hematoxylin and eosin staining were performed to observe tumor formation and bone damage. Our results suggested that Hsp90 expression in mice with breast cancer metastasis in the spine was significantly higher than that in normal mice. Furthermore, Hsp90 expression was decreased and the spinal metastasis from breast cancer was inhibited by 17-AAG application. Hsp90 could be considered as an indicator to forecast tumor metastasis and provide a target for the treatment of spinal metastasis of breast cancer.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Benzoquinones / pharmacology*
  • Blotting, Western
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation / drug effects
  • Female
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Lactams, Macrocyclic / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Neoplasms / drug therapy
  • Spinal Neoplasms / metabolism
  • Spinal Neoplasms / secondary*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • RNA, Messenger
  • tanespimycin