Thermotolerance and sensitivity of human cancer cells to cisplatin and doxorubicin

Richards, EH; Begum, TA; Masters, Jrw

doi:10.3892/ijo.8.6.1265

Cited by 2 publications

(2 citation statements)

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“…Supporting this observation, hsp27 has been found to contribute to increased drug resistance in Chinese hamster ovary (CHO) cells [Lavoie et al, 1993], colon cancer cells [Garrido et al, 1996], and testis cancer cells [Richards et al, 1996]. More recently, we have found that elevated hsp27 levels also correlate with increased invasion of human breast cancer cells [Lemieux et al, 1996].…”

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confidence: 49%

Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells

et al. 1997

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Since the small heat shock protein hsp27 enhances both growth and drug resistance in breast cancer cells, and is a bad prognostic factor in certain subsets of breast cancer patients, we have characterized the transcriptional regulation of hsp27, with the long-term goal of targeting its expression clinically. The majority of the promoter activity resides in the most proximal 200 bp. This region contains an imperfect estrogen response element (ERE) that is separated by a 13-bp spacer that contains a TATA box. Gel-shift analysis revealed the binding of a protein (termed HET for Hsp27-ERE-TATA-binding protein) to this region that was neither the estrogen receptor nor TATA-binding protein. We cloned a complete cDNA (2.9 kb) for HET from an MCF-7 cDNA library. To confirm the identity of the HET clone, we expressed a partial HET clone as a glutathione S-transferase fusion protein, and showed binding to the hsp27 promoter fragment in gel-retardation assays. The HET clone is almost identical to a recently published scaffold attachment factor (SAF-B) cloned from a HeLa cell cDNA library. Scaffold attachment factors are a subset of nuclear matrix proteins (NMP) that interact with matrix attachment regions. Analyzing how HET could act as a regulator of hsp27 transcription and as a SAF/NMP, we studied its subnuclear localization and its effect on hsp27 transcription in human breast cancer cells. We were able to show that HET is localized in the nuclear matrix in various breast cancer cell lines. Furthermore, in transient transfection assays using hsp27 promoter-luciferase reporter constructs, HET overexpression resulted in a dose-dependent decrease of hsp27 promoter activity in several cell lines.

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confidence: 49%

Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells

et al. 1997

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“…Additionally, it was reported that heat-induced carboplatin resistance of hepatoma cells is mediated by HSPA1 [ 96 ]. Nevertheless, there are also reports that the activation of HSPs expression did not enhance the survival of different cancer cells during cisplatin or colchicine, 5-fluorouracil, actinomycin D, and methotrexate treatment [ 90 , 91 , 97 - 99 ]. Moreover, diminished HSPs expression resulting from HSF1 silencing did not abrogate the resistance of HeLa cells to cisplatin [ 100 ] or MeWo cells to dacarbazine [ 101 ].…”

Section: Hsf1 and Drug Resistance Of Cancermentioning

confidence: 99%

Pleiotropic Role of HSF1 in Neoplastic Transformation

Vydra¹,

Toma

Widłak³

2014

CCDT

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HSF1 (Heat Shock transcription Factor 1) is the main transcription factor activated in response to proteotoxic stress. Once activated, it induces an expression of heat shock proteins (HSPs) which enables cells to survive in suboptimal conditions. HSF1 could be also activated by altered kinase signaling characteristic for cancer cells, which is a probable reason for its high activity found in a broad range of tumors. There is rapidly growing evidence that HSF1 supports tumor initiation and growth, as well as metastasis and angiogenesis. It also modulates the sensitivity of cancer cells to therapy. Functions of HSF1 in cancer are connected with HSPs’ activity, which generally protects cells from apoptosis, but also are independent of its classical targets. HSF1-dependent regulation of non-HSPs genes plays a role in cell cycle progression, glucose metabolism, autophagy and drug efflux. HSF1 affects the key cell-survival and regulatory pathways, including p53, RAS/MAPK, cAMP/PKA, mTOR and insulin signaling. Although the exact mechanism of HSF1 action is still somewhat obscure, HSF1 is becoming an attractive target in anticancer therapies, whose inhibition could enhance the effects of other treatments.

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Thermotolerance and sensitivity of human cancer cells to cisplatin and doxorubicin

Cited by 2 publications

References 4 publications

Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells

Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells

Pleiotropic Role of HSF1 in Neoplastic Transformation

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