Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the p53 protein, resulting from gene mutations that increase protein stability, has been detected in greater than 25% of primary human breast cancers. In addition, approximately 10% of breast cancer patients have circulating antibodies to the p53 protein. In this study, the anti-p53 humoral response is correlated with the presence and type of mutant p53 protein expressed in the tumor. In a series of 60 breast cancer patients, 0 of 30 tumors with normal, low-level p53 expression induced anti-p53 antibodies, whereas 7 (23%) of 30 tumors with p53 overexpression elicited a specific anti-p53 antibody response. These 7 patients had anti-p53 antibodies that recognized wild-type p53 and a variety of mutant p53 proteins. A comparison of p53 mutations revealed that antibody-negative tumors had mutations exclusively in exons 7 and 8, whereas antibody-positive tumors had mutations primarily in exons 5 and 6. Moreover, all antibody-eliciting tumors contained complexes between p53 and a 70-kDa heat shock protein, whereas none of the antibody-negative tumors contained this complex. This study implicates a 70-kDa heat shock protein in the antigenic presentation of p53.
 ...
PMID:Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers. 137

Previous studies have shown that certain chemotherapeutic drugs are less effective on tumor cells when cells have been previously exposed to hyperthermia. In the present study, we have evaluated whether specific modifications in heat shock protein (hsp) expression are associated with resistance to anticancer drugs. RNA levels for hsp90, hsp70, and hsp27 were studied by Northern and slot blots, while proteins were studied by two-dimensional gel electrophoresis, in MCF-7/BK and MDA-MB-231 breast cancer cells. The sensitivities of these cells to doxorubicin, colchicine, 5-fluorouracil, cisplatin, actinomycin D, and methotrexate were tested by clonogenic assays. These techniques were applied to both cell lines before (control) and after heat shock. The study revealed that elevated hsp70 and hsp27 levels were associated with doxorubicin resistance. In addition, the presence of phosphorylated hsp27 isoforms was also associated with doxorubicin resistance. The study showed that elevated hsps were not associated with multidrug resistance. Heat shock did not induce P170 glycoprotein mRNA overexpression or resistance to the other drugs tested. We also found that the level of doxorubicin protection conferred by the overexpression of hsp was lower than that obtained in cells expressing a multidrug resistance phenotype (MDA-A1R cells). In these cells, heat shock did not confer additional doxorubicin resistance and hsp27 phosphorylation was deficient. Our studies suggest that specific hsps are associated with doxorubicin resistance in certain human breast cancer cells and that this mechanism seems to be independent of the multidrug resistance system.
 ...
PMID:Response of human breast cancer cells to heat shock and chemotherapeutic drugs. 161 38

Previous studies have shown several similarities between an estrogen-regulated heat shock protein of 24,000-28,000 daltons (hsp27), and a cytoplasmic estrogen receptor-associated protein of 27,000-29,000 daltons (p29). These proteins have been studied by monoclonal antibodies generated in different laboratories. In the present report we have performed immunocytochemical and immunoblot studies to explore if the monoclonal antibodies against hsp27 (C11) and against p29 (ER-D5) may be identifying the same protein. Breast and endometrial carcinomas and normal endometrial samples were examined by immunocytochemistry (in mirror sections and by double-immunostaining). Identical hsp27 and p29 immunostaining intensity, distribution, and percentage of stained cells was demonstrated by immunocytochemistry. The antigens examined by the two antibodies appeared in the same cells. Cytosols from tumors analyzed by the Western blot technique revealed that the C11 and the ER-D5 antibodies recognized bands with identical electrophoretic mobility. Immunoprecipitation studies with one antibody, C11, followed by Western blot showed that the precipitate was reactive with both antibodies. Identical C11 and ER-D5 reacting spots were observed after blotting proteins separated by high resolution two-dimensional gel electrophoresis. In addition, p29 protein was induced by heat shock in the estrogen receptor negative MDA-MB-231 human breast tumor cell line. These results strongly suggest that the two proteins under investigation are identical.
Breast Cancer Res Treat 1991 Dec
PMID:Immunological evidence for the identity between the hsp27 estrogen-regulated heat shock protein and the p29 estrogen receptor-associated protein in breast and endometrial cancer. 166 87

In this study we have demonstrated that dimerization of mammalian progesterone receptors (PR) occurs in the absence of DNA. A specific immune coisolation assay was performed on extracts of T-47D human breast cancer cells with a monoclonal antibody specific for the full-length B form of progesterone receptor (PR-B). This resulted in coisolation of significant amounts of truncated form-A receptors (PR-A), indicating the presence of stable PR-A.PR-B dimers in solution. A positive correlation was observed between the ability of different receptor forms to oligomerize in solution and their ability to bind to specific DNA sequences. The ability to form stable PR-A.PR-B oligomers in the absence of DNA was also found to correlate with release of 90-kDa heat shock protein (hsp90) from the unactivated PR complex. These results support the hypothesis that dimerization in the absence of DNA is an important mechanism controlling receptor DNA-binding function and that hsp90 release may be a key step regulating dimerization. This suggests that hsp90 may function to repress DNA-binding activity indirectly by blocking receptor dimerization.
 ...
PMID:Dimerization of mammalian progesterone receptors occurs in the absence of DNA and is related to the release of the 90-kDa heat shock protein. 198 83

We have studied by immunocytochemistry and monoclonal antibodies the presence and localization of estrogen receptors, progesterone receptors, and a 24-kD estrogen-regulated heat shock protein in biopsies from breast and endometrial cancer patients. Three different tissue processing protocols were used to colocalize the antigens in the same tissue sections: a) frozen sections, b) formalin fixation with routine paraffin embedding, and c) picric acid-formaldehyde (PAF) fixation with a rapid embedding in paraffin. Frozen sections showed good receptor staining but poor 24-kD protein immunoreactivity, while routine paraffin sections (with or without DNase pretreatment) were inadequate to reveal the nuclear receptor proteins at the same level seen in frozen sections. On the other hand, all three proteins could be detected satisfactorily in PAF-fixed paraffin-embedded tissue. Using this procedure we were able to visualize 24-kD protein and estrogen receptor or progesterone receptor in individual cells in paraffin sections. The study revealed that in all of the estrogen receptor positive breast and endometrial tumor samples, almost 90% of the cells expressing the cytoplasmic 24-kD protein contained estrogen receptor in the cell nucleus. In contrast, 24-kD immunoreactive cells did not express progesterone receptors in almost 40% of the progesterone receptor positive tumor samples.
Breast Cancer Res Treat 1990 Oct
PMID:Colocalization of estrogen and progesterone receptors with an estrogen-regulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue. 208 75

Untransformed cytosol receptors for progesterone (PR), androgen (AR), estrogen (ER), and glucocorticosteroid (GR) in rabbit tissues contain a 59-kDa protein (p59) (Tai, P.K.K., Maeda, Y., Nakao, K., Wakim, N.G., Duhring, J.L., and Faber, L.E. (1986) Biochemistry 25, 5269-5275) and a 90-kDa heat shock protein (hsp90). In the present study, receptors from calf uterus (PR, AR, ER, and GR) and from human breast cancer MCF7 cells (PR and GR) were also shown to be comprised of hsp90 and p59. These heterooligomer receptor complexes were stabilized both by transition metal oxyanions (molybdate and tungstate) and chemical cross-linking with dimethylpimelimidate. In 0.4 M KCl, tungstate-stabilized (but not molybdate-stabilized) PR, AR, ER, and GR retained hsp90, but lost p59. Dimethylpimelimidate cross-linking prevented p59 dissociation from hsp90-receptor complexes. Stabilization with tungstate and/or cross-linking permitted immunoaffinity purification of untransformed rabbit as well as calf PR and ER on EC1-Affi-Gel 10 column (an anti-p59 immunoadsorbant). Combined immunoaffinity purification and cross-linking experiments indicated that p59 is bound to hsp90 in the cytosol. We propose that in the nontransformed steroid receptor, p59 interacts with hsp90 rather than with the hormone binding subunit.
 ...
PMID:The non-DNA-binding heterooligomeric form of mammalian steroid hormone receptors contains a hsp90-bound 59-kilodalton protein. 235 20

The M(r) 27,000 heat shock protein (hsp27) is a member of the small heat shock protein family. Cell differentiation is a process in which a role for small heat shock proteins has been suggested. The ability to control the state of differentiation in normal human keratinocytes by modification of extracellular calcium concentration makes it an ideal in vitro system for exploration of the specific components and steps in differentiation. We have focused on the in vitro expression of hsp27 in undifferentiated and differentiated human normal keratinocytes (HNK) as a marker for differentiation. Immunological methods (immunohistochemistry and immunoblotting) as well as Northern blotting were used. Cells of the breast cancer line MCF-7 served as a positive control. We demonstrated that hsp27 was expressed at low levels in normal human keratinocytes, kept under calcium concentrations where cells formed discrete colonies of undifferentiated, noncornified cuboidal cells (0.03 mM Ca2+), and linked cuboidal cells with a noncornified appearance (0.15 mM Ca2+). Upon cultivation in high calcium (1.00 mM Ca2+) where a more morphological state of differentiation was reached, more spindle shaped with cornification of individual cells, a 2-fold increase in hsp27 expression was observed. A somewhat weaker increase in hsp27 mRNA was shown by Northern blot analysis. Our studies provide evidence that hsp27 is accumulated in a differentiation-dependent manner in human normal keratinocytes grown under conditions inducing terminal differentiation (0.03-1.00 mM Ca2+). Therefore, hsp27 can be regarded as a marker of differentiation in human normal keratinocytes.
 ...
PMID:Increased expression of the M(r) 27,000 heat shock protein (hsp27) in in vitro differentiated normal human keratinocytes. 752 31

We present evidence that the mechanisms controlling induction of heat shock transcription factors (HSFs) and mRNA expression of the 27,000 molecular weight heat shock protein, hsp27, are diverse in human breast cancer cells. Heat shock accumulation of hsp27 RNA is associated with the activation of HSF in MDA-MB-231 cells. We have later passage MCF-7 breast cancer cell lines with elevated, constitutive expression of hsp27 mRNA, perhaps due to hsp27 gene amplification. Estradiol and heat shock treatment no longer affect the level of hsp27 mRNA in these cells. Heat induction of HSF is inhibited in cells overexpressing hsp27, although metal ions and amino acid analogs are still capable of activating HSF. These cells will provide a useful system for characterizing alternative pathways in HSF inhibition and activation.
Breast Cancer Res Treat 1994
PMID:Constitutive overexpression of the 27,000 dalton heat shock protein in late passage human breast cancer cells. 786 47

The authors studied the role of 70-Kd heat shock protein (HSP70) in the progression of breast cancer by examining the correlation between the expression of HSP70 and epidermal growth factor receptor, c-erbB-2, p53, and estrogen receptor in 124 cases of invasive primary human breast cancers. Positivity of an anti-HSP70 monoclonal antibody, C92, was closely associated with the elevation of estrogen receptor (P < .008), whereas it inversely correlated with the expression of p53 (P < .01). In addition, the expression of HSP70 correlated inversely with the expression of epidermal growth factor receptor, although the correlation was not statistically significant (P = .06). These results suggest that the expression of HSP70 plays a role in the progression of human breast cancer.
 ...
PMID:Correlation of heat shock protein 70 expression with estrogen receptor levels in invasive human breast cancer. 790 91

This paper describes a prospective immunohistochemical analysis of 27 kDa heat shock protein (HSP27) in 361 patients with primary breast cancer in relation to disease-free survival (DFS) and survival from first relapse (SR). Oestradiol (ER) and progesterone (PR) receptors were also quantitated and related to the HSP27 data. While ER positively predicted a good outcome for both DFS and SR, HSP27 positivity predicted a prolonged SR but short DFS. The association between HSP27 and DFS only attained statistical significance in node-negative patients. Subgroup analysis reinforced the complementary relationship of HSP27 and ER for SR and opposing influences for DFS. In both node-negative and node-positive women, ER+ HSP27- patients had a longer DFS than ER- HSP27+ counterparts. There was no relationship between HSP27 and overall survival. HSP27 staining was highly correlated with ER but not PR, patient age, tumour size or menstrual status. There was a marginal correlation (P = 0.04) with histological grade with well-differentiated tumours having the highest HSP27. Cox multivariate regression analysis of the contribution of HSP27 in the presence of data on ER, PR, stage, nodal status and histological grade indicated that HSP27 was not of independent prognostic importance for DFS or overall survival and was only of borderline significance for OS (P < 0.07). However, in the absence of ER and PR data, HSP27 staining is an effective way of getting the same prognostic information. HSP27 staining appears to correlate with different biological features in early and advanced breast, high HSP27 being linked with short DFS in node-negative patients but with prolonged survival from first recurrence.
 ...
PMID:A 27 kDa heat shock protein that has anomalous prognostic powers in early and advanced breast cancer. 814 64


1 2 3 4 5 6 7 8 9 10 Next >>