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Clinical and biological significance of HSP89 alpha in human breast cancer
Author(s) -
Jameel A.,
Skilton R. A.,
Campbell T. A.,
Chander S. K.,
Coombes R. C.,
Luqmani Y. A.
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910500315
Subject(s) - breast cancer , prolactin , heat shock protein , biology , malignancy , medicine , endocrinology , breast disease , messenger rna , tamoxifen , cancer research , cancer , hormone , gene , biochemistry
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, AJ I, 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. AJ I 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, AJ I 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 AJ I mRNA levels. The increasing evidence for the association of heat‐shock proteins with steroid receptors suggests that Aj I may play an important role in the control of estrogen‐receptor transcriptional activity in breast cancers.