Clinical and Biological Significance of HSP89 Alpha in Human Breast Cancer

Int J Cancer. 1992 Feb 1;50(3):409-15. doi: 10.1002/ijc.2910500315.

Abstract

In order to isolate and characterize genes whose expression may be altered in breast malignancy, we screened a cDNA library with a polyclonal anti-serum against breast-cancer-metastasis membranes and isolated several immunopositive clones. One of these, AJ1, was analyzed in detail and found to be expressed at varying levels as a 3.3-kb mRNA in all of 143 breast cancers. High expression was associated with lymph-node involvement (p = 0.03). Comparison between high- and low-expressing groups showed a significant difference at 4 and 6 years for both overall (p = 0.004 and p = 0.002 respectively) and disease-free (p = 0.0001 and p = 0.04 respectively) survival, but not at 11 years. AJ1 was expressed at much lower levels in non-malignant biopsies as compared with malignant tissue (p = 0.001). Expression was observed in breast-cancer cell lines MCF-7, ZR-75-1, T47D, MDA-MB-231 and HBL 100. Partial sequence analysis of the 620 bp clone showed complete homology with human heat-shock protein 89 alpha. In addition to being heat-inducible in all the breast cell lines examined, AJ1 levels were increased by estradiol (blocked by cyclohexamide and tamoxifen), EGF, oxytocin and vasopressin in a time-dependent manner in MCF-7 cells and by estradiol, EGF, prolactin and hydrocortisone in T47D cells. In MDA-MB-231 cells, EGF caused down-regulation of AJ1 mRNA levels. The increasing evidence for the association of heat-shock proteins with steroid receptors suggests that AJ1 may play an important role in the control of estrogen-receptor transcriptional activity in breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Breast Neoplasms / genetics*
  • Epidermal Growth Factor / pharmacology
  • Estradiol / pharmacology
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Heat-Shock Proteins / genetics*
  • Humans
  • Hydrocortisone / pharmacology
  • Oxytocin / pharmacology
  • Prolactin / pharmacology
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Tamoxifen / pharmacology
  • Tumor Cells, Cultured
  • Vasopressins / pharmacology

Substances

  • Heat-Shock Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Tamoxifen
  • Vasopressins
  • Estradiol
  • Oxytocin
  • Epidermal Growth Factor
  • Prolactin
  • Hydrocortisone