Biological and Clinical Implications of Heat Shock Protein 27000 (Hsp27): a Review

Abstract

Heat shock and other environmental and pathophysiologic stresses stimulate synthesis of heat shock proteins (Hsps). These proteins enable the cell to survive and recover from stressful conditions by as yet uncompletely understood mechanisms. Hsp27 is an important small Hsp (molecular weight, 27,000) found in human cells--both cancer cells and normal cells. This protein, besides its putative role in thermotolerance, is of special clinical interest because of recent data suggesting it may also play a role in drug resistance. In adults, Hsp27 is found particularly in several cell types such as breast, uterus, cervix, placenta, skin, and platelets. Although low-molecular-weight (small) Hsps have been found to be involved in embryogenesis of Xenopus and Drosophila, they have not been detected in human fetal organs. Regulation of expression of the Hsp gene (also known as HSPB1) has been considered a paradigm of gene regulation and is actively being studied in both prokaryotes and eukaryotes. In prokaryotes, the major Hsp genes are transcriptionally regulated by positively and negatively acting transcription factors. In eukaryotes, the genes encoding Hsps contain a regulatory DNA motif (inverted repeats of the pentameric sequence nGAAn) known as the heat shock element. Hsp27 may function as a molecular chaperone and in signal transduction pathways of different cell regulators, and Hsp27 and other Hsps may be active in development of resistance to stressful conditions and agents including cytotoxic drugs. Study findings indicate that some but not all estrogen-positive breast cancers express Hsp27, and overexpression of Hsp27 has been associated with both good and poor prognosis. In endometrial carcinomas, the presence of Hsp27 is correlated with the degree of tumor differentiation as well as with the presence of estrogen and progesterone receptors. Studies suggest, however, that detection of Hsp27 should not be considered to be a method for identifying hormone-responsive tumors or detecting estrogen receptors. Hsp27 seems to be a biochemical marker of estrogenic endometrial response. In patients with cervical cancer, Hsp27 is predominantly expressed in well-differentiated and moderately differentiated squamous cell carcinomas. In addition, expression of Hsp27 seems to be a negative prognostic factor for gastric cancer. Different isoforms of Hsp27 have been found in lymphoid tissue of patients with acute lymphoblastic leukemia, and the protein has also been associated with viral infections. These aspects are summarized and discussed in the present review.

Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells

“…Hsp27 expression is increased in a variety of malignancies, including prostate (6), breast (7), gastric (8), ovarian (9), and bladder cancers (10,11). Furthermore, Hsp27 overexpression has been associated with multidrug resistance (12) and direct inhibition of apoptosis (13,14) and is functionally linked to increased tumorigenicity and treatment resistance in breast (15) and colon (16) cancers.…”

Do heat shock proteins have a role in breast cancer?

“…Expression of hsps in breast cancer Hsp27 Hsp27 has been isolated by different laboratories as a 25 kDa protein associated with actin polymerisation, P24, an oestrogen-associated protein and as a 25 kDa growth-related protein (Ciocca et al, 1993a;Miron et al, 1991). Hsp27 was initially identified as an oestrogen-binding protein in human breast cancer cell lines (Edwards et al, 1981).…”

Expression of heat shock protein 70 in the liver of extensively and intensively kept heavy pigs

“…Interestingly, although many studies have evaluated HSP response to acute and chronic stress conditions (heat, hypoxia, infections;Ciocca et al, 1993;Hartman and Gething, 1996;Voellmy, 1996), the possible role of HSP in animal response to rearing conditions has been poorly investigated. Particularly in pigs, no study has been conducted to evaluate the effect of the rearing system on HSP expression.…”

“…In mammals, the constitutive HSP family members (HSC70) play an important chaperoning role in unstressed cells, whereas the expression of the inducible (HSP70) forms is known to be activated by acute stressor insults (Morimoto et al, 1990) and pathological and environmental factors (Kiang and Tsokos, 1998), including psychological stress (Fukudo et al, 1997). HSPs, especially HSP70, can interact with denatured or misfolded proteins and assist in their recovery from stressful events, either by repairing (protein refolding) or degrading them (Ciocca et al, 1993;Hartman and Gething, 1996;Voellmy, 1996).…”

“…In mammals, the constitutive HSP family members (HSC70) play an important chaperoning role in unstressed cells, whereas the expression of the inducible (HSP70) forms is known to be activated by acute stressor insults (Morimoto et al, 1990) and pathological and environmental factors (Kiang and Tsokos, 1998), including psychological stress (Fukudo et al, 1997). HSPs, especially HSP70, can interact with denatured or misfolded proteins and assist in their recovery from stressful events, either by repairing (protein refolding) or degrading them (Ciocca et al, 1993;Hartman and Gething, 1996;Voellmy, 1996).A significant decrease in the levels of HSP70, one of the most important HSPs, was reported in the liver of acutely stressed male rats, whereas only a weak decrease in the levels of HSP70 was demonstrated in chronic stress models (Filipović et al, 2008). Moreover, the overexpression of HSP70 in the stomach of male rats seemed to protect against gastric ulcers, through its cytoprotective effects on the gastric mucosa, by increasing mucosal blood flow (Shichijo et al, 2003).…”