Anti-sense inhibition of small-heat-shock-protein (HSP27) expression in MCF-7 mammary-carcinoma cells induces their spontaneous acquisition of a secretory phenotype

Horman, Sandrine; Fokan, Dominique; Mosselmans, Roger; Mairesse, Nicole; Galand, Paul

doi:10.1002/(sici)1097-0215(19990812)82:4<574::aid-ijc17>3.0.co;2-l

Cited by 22 publications

(12 citation statements)

References 26 publications

(36 reference statements)

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“…Our findings suggest that if HSP27 contributes to the thermoresistance of the DU-145 wtBRCA1 cell clones, it is sufficient that HSP27 protein levels are elevated at the time the heating begins; and mechanisms unrelated to BRCA1 act to maintain the protein levels of HSP27 during heating. Several additional studies have also suggested roles for HSP27 in the regulation of cell differentiation, cell proliferation, and actin polymerization (Miron et al, 1991;Benndorf et al, 1994;Mairesse et al, 1996;Horman et al, 1999). For example, HSP27 regulated the process of F actin polymerization in biochemical assays, depending upon the degree of phosphorylation and oligomerization of the HSP27 protein (Miron et al, 1991;Benndorf et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Role of BRCA1 in heat shock response

et al. 2003

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The heat shock response is an evolutionarily conserved response to heat and other stresses that promotes the maintenance of key metabolic functions and cell survival. We report that exposure of human prostate (DU-145) and breast (MCF-7) cancer cells to heat (421C) caused a rapid disappearance of the breast cancer susceptibility gene-1 (BRCA1) protein, starting at E1 h after the onset of heating and slightly lagging behind the increase in heat shock protein 70 (HSP70) levels. The heat-induced loss of BRCA1 occurred at the protein level, since: (1) BRCA1 mRNA expression was unaffected; and (2) the BRCA1 protein loss was also observed in DU-145 cells that expressed exogenous wild-type BRCA1 (wtBRCA1). In addition to heat regulation of BRCA1 protein levels, we also found that BRCA1 could modulate the heat shock response. Thus, wtBRCA1 overexpressing DU-145 cell clones showed significantly decreased sensitivity to heatinduced cytotoxicity; and Brca1 mutant mouse embryo fibroblasts showed increased sensitivity to heat. The DU-145 wtBRCA1 clones also showed increased expression of the small heat shock protein HSP27; and reporter assays revealed that wtBRCA1 stimulated a two to four-fold increase in HSP27 promoter activity, consistent with its ability to upregulate HSP27 mRNA and protein levels. In studies using epitope-tagged truncated BRCA1 proteins, the ability to stimulate the HSP27 promoter and to mediate heat-induced degradation required the aminoterminus but not the carboxyl-terminus of BRCA1. Although the heat-induced loss of BRCA1 appeared to be due to protein degradation, various protein metabolic agents (or combinations) failed to block this event, including: MG132 (a 26S proteasomal inhibitor), Nacetyl-leucyl-leucyl-norleucinal (a calpain inhibitor), z-VAD-fmk (a pan-caspase inhibitor), and ammonium chloride and chloroquine (which stabilize lysosomes). These findings suggest that in addition to its other functions, BRCA1 may participate in mammalian heat shock response pathways.

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Section: Discussionmentioning

confidence: 99%

Role of BRCA1 in heat shock response

et al. 2003

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“…10 In this report, we also showed the overexpression of hsp27, a member of the small heat shock protein family that is overexpressed in DMBA-induced mammary carcinomas, 27 and has been linked to an inhibition of differentiation in MCF-7 breast cancer cells. 11 Furthermore, during the initiation and promotion of human breast cancers, the expression of hsp27 increases. 28 The finding that a number of heat shock proteins are overexpressed in the early stages of carcinogenesis with DMBA (shown here) as well as with PhIP 5 further implicates heat shock proteins in breast cancer development.…”

Section: Discussionmentioning

confidence: 99%

“…One group of genes included the heat shock proteins hsp84, hsp86 and hsp27 that have been implicated in breast cancer growth or epithelial cell proliferation. 10,11 At the 6-week time point, an increased expression of hsp86 and hsp27 Those selected for further analysis.…”

Section: Confirmation Of Gene Expression Profilesmentioning

confidence: 99%

Gene expression profiling in the mammary gland of rats treated with 7,12‐dimethylbenz[a]anthracene

Papaconstantinou

Shanmugam

Shan

et al. 2005

Intl Journal of Cancer

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Identification of molecular markers of early‐stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12‐dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real‐time PCR, RT‐PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of β‐casein and transferrin and higher expression of hsp27 in glands from DMBA‐treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki‐67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, α‐tubulin and hsp27, were all overexpressed in the mammary gland of DMBA‐treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development. Published 2005 Wiley‐Liss, Inc.

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“…Several key players in cell cycle control systems are known to undergo transient association with chaperones [67]. However, it is not yet definitely assessed whether this association may stimulate or hamper proliferation: for example, transfection of HSP27 to a breast carcinoma cell line led to a slower proliferation [68], whereas antisense inhibition of HSP27 in MCF-7 cells inhibited growth [69], and induced the acquisition of a secretory phenotype [70]. Besides, overexpression of HSP27 in rat colon carcinoma cell clones [71] and in breast cancer cells [72] enhanced their tumorigenicity, as extensively reviewed by Helmbrecht and Colleagues and briefly resumed in Table 3 [67].…”

Section: Cancermentioning

confidence: 99%

In Silico Analyses of Proteomic Data Suggest a Role for Heat Shock Proteins in Umbilical Cord Blood Hematopoietic Stem Cells

D’Alessandro

Grazzini

Giardina

et al. 2010

Stem Cell Rev and Rep

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Umbilical-cord blood (UCB) has growingly become an accepted alternative source of hematopoietic stem cells for transplantation purposes. However, the low cell dose limit within a single unit is still an obstacle hindering the way of a broader diffusion. The real deal is the lack of knowledge about the molecular processes governing the events of expansion and differentiation of these cells. In order to fill this void, several studies were focused on the identification of the peculiar whole protein profile of UCB-derived hematopoietic stem cells. In this review article we provide a referenced list of overall proteins from UCB-derived hematopoietic stem and progenitor cells. This list has been elaborated for pathway and network analyses, along with GO term enrichment for biological and molecular functions, in order to individuate main classes of proteins governing functioning of these cells. From these analyses it seems to emerge a central role for heat shock proteins in immature hematopoietic stem cells. Their role might be relevant in protecting crucial transcription factors which drive proliferation and differentiation towards a specific lineage (e.g. erythroid, myeloid). Hereby we also stress the helpfulness of interactomics elaboration in providing a unified overview of independent proteomics data. It appears that maturation, other than representing a bottleneck to protein expression, could sculpt interaction maps via reducing complexity of immature interactomics profiles.

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Anti-sense inhibition of small-heat-shock-protein (HSP27) expression in MCF-7 mammary-carcinoma cells induces their spontaneous acquisition of a secretory phenotype

Cited by 22 publications

References 26 publications

Role of BRCA1 in heat shock response

Role of BRCA1 in heat shock response

Gene expression profiling in the mammary gland of rats treated with 7,12‐dimethylbenz[a]anthracene

In Silico Analyses of Proteomic Data Suggest a Role for Heat Shock Proteins in Umbilical Cord Blood Hematopoietic Stem Cells

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