A novel association between the human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma.
A search for differentially expressed genes in a pair of nonmetastatic (PC-3) versus metastatic variant (PC-3M) human prostate carcinoma cell lines led to identification of the human heat shock factor (HSF1) as an overexpressed gene product in PC-3M cells. Analysis of primary prostate cancer specimens indicated that HSF1 is generally up-regulated in most of the malignant prostate epithelial cells relative to the normal prostate cells. Among the known effectors of HSF1 action, constitutive levels of HSP70 and HSP90 are not significantly altered by the naturally elevated expression of HSF1 as in PC-3M cells or by transduced overexpression of HSF1 in PC-3 cells. The basal levels of HSP27 in both cases are, however, consistently increased by two- to threefold. With respect to response to heat shock, high basal concentration of HSP90 is not further enhanced in these cells, and HSP70 is up-regulated irrespective of HSF1 level. Heat shock, however, causes an increase in HSP27 when HSF1 is up-regulated, except when the expression of HSF1 is already too high. These results document for the first time that HSF1 is overexpressed in human prostate cancer cells, at least one consequence of which in the prostate cancer cell lines tested is stimulation of both basal and stress-induced expression of HSP27, an important factor in cell growth, differentiation, or apoptosis.
Hoang
A T
AT
Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033, USA.
Huang
J
J
Rudra-Ganguly
N
N
Zheng
J
J
Powell
W C
WC
Rabindran
S K
SK
Wu
C
C
Roy-Burman
P
P
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D015152:Blotting, Northern; D015153:Blotting, Western; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D014157:Transcription Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors