Clinical and biological significance of HSP89 alpha in human breast cancer.
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.
Jameel
A
A
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Skilton
R A
RA
Campbell
T A
TA
Chander
S K
SK
Coombes
R C
RC
Luqmani
Y A
YA
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014667:Vasopressins / Q000494:pharmacology
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013629:Tamoxifen; D014667:Vasopressins; D004958:Estradiol; D010121:Oxytocin; D004815:Epidermal Growth Factor; D011388:Prolactin; D006854:Hydrocortisone