Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo

Abstract

Heat shock proteins (HSPs) are thought to play a role in the development of cancer and to modulate tumor response to cytotoxic therapy. In this study, we have examined the expression of hsf and HSP genes in normal human prostate epithelial cells and a range of prostate carcinoma cell lines derived from human tumors. We have observed elevated expressions of HSF1, HSP60, and HSP70 in the aggressively malignant cell lines PC-3, DU-145, and CA-HPV-10. Elevated HSP expression in cancer cell lines appeared to be regulated at the post-messenger ribonucleic acid (mRNA) levels, as indicated by gene chip microarray studies, which indicated little difference in heat shock factor (HSF) or HSP mRNA expression between the normal and malignant prostate cell lines. When we compared the expression patterns of constitutive HSP genes between PC-3 prostate carcinoma cells growing as monolayers in vitro and as tumor xenografts growing in nude mice in vivo, we found a marked reduction in expression of a wide spectrum of the HSPs in PC-3 tumors. This decreased HSP expression pattern in tumors may underlie the increased sensitivity to heat shock of PC-3 tumors. However, the induction by heat shock of HSP genes was not markedly altered by growth in the tumor microenvironment, and HSP40, HSP70, and HSP110 were expressed abundantly after stress in each growth condition. Our experiments indicate therefore that HSF and HSP levels are elevated in the more highly malignant prostate carcinoma cells and also show the dominant nature of the heat shock-induced gene expression, leading to abundant HSP induction in vitro or in vivo.

Targeting Cdc37 Inhibits Multiple Signaling Pathways and Induces Growth Arrest in Prostate Cancer Cells

“…4C). We used the antibody Ab46-4 that detects a number of HSP70 family members, including the constitutive protein HSC70 that migrates with an apparent M r of 73 kDa and the stress-inducible 72-kDa isoform HSP72, which is also present at basal levels in prostate cancer cells (31). In cells depleted of Cdc37, both baseline and 17AAG-stimulated levels of the HSP72 isoform are greatly reduced, although expression of the more slowly migrating HSC70 is not affected (Fig.…”

“…HSP70 induction through HSP90 inhibition involves the transcription factor HSF1 (heat shock factor 1), a sequence-specific factor that regulates expression of HSP genes through response elements in their promoters (HSE; ref. 31). For these experiments, we employed a promoter-luciferase reporter construct based on the HSP70B gene, an HSP70 family gene that is activated by HSF1 with high specificity.…”

State of heat shock factor 1 expression as a putative diagnostic marker for oral squamous cell carcinoma

“…Many types of tumors express high concentrations of HSPs, which are correlated with increases in HSF1 levels (8)(9)(10)(11). Elevated levels of HSP expression contribute directly to tumorigenesis through inhibition of programmed cellular death in tumors (10,12), and thus protect cancer cells from chemotherapy and radiation therapy (9,(13)(14)(15)(16)(17). HSF1 exists as a monomeric protein in the cytoplasm.…”

Hsp60 Regulation of Tumor Cell Apoptosis

“…However, whether Hsp60 also contributes to cell survival is controversial, with data suggesting a pro-apoptotic function via enhanced caspase activation (13,14) or, conversely, an anti-apoptotic mechanism involving sequestration of Bax-containing complexes (15). A role of Hsp60 in cancer is equally uncertain, as up-regulation (16,17) or down-regulation (18,19) of this chaperone has been reported in various tumor series correlating with disease outcome.…”