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Sent on Saturday, 2007 Sep 29.
Search breast cancer
Click on the following url to view complete results in pubmed. (Results may change over time.)
http://www.ncbi.nlm.nih.gov/entrez/cubby.fcgi?call=0Y_DxfGRAN8QluRUFcIUJKxGTHZSWgHOVOr7FSjyfHY1jhTYyjASzkEXbwQQGJ9&WebCubbyUser=0J7yA6-hWl1pfuo5Mlw3eJA2%401EDE72626FF02620_0005SID
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==================== Entrez pubmed Results ======================
Items 1 - 5 of 50
1: Breast Cancer Res Treat. 2007 Sep 28; [Epub ahead of print]
Fatty acid metabolism in breast cancer cells: differential inhibitory effects of
epigallocatechin gallate (EGCG) and C75.
Puig T, Vazquez-Martin A, Relat J, Petriz J, Menendez JA, Porta R, Casals G,
Marrero PF, Haro D, Brunet J, Colomer R.
Fundacio d'Investigacio Biomedica de Girona Dr. Josep Trueta (IdIBGi), Hospital
Universitari de Girona Dr. Josep Trueta, Girona, Spain.
Endogenous fatty acid metabolism is crucial to maintain the cancer cell
malignant phenotype. Lipogenesis is regulated by the enzyme fatty acid synthase
(FASN); and breakdown of fatty acids is regulated by carnitine
palmitoyltransferase-1 (CPT-I). FASN is highly expressed in breast cancer and
most common human carcinomas. Several compounds can inhibit FASN, although the
degree of specificity of this inhibition has not been addressed. We have tested
the effects of C75 and (-)-epigallocatechin-3-gallate (EGCG) on fatty acid
metabolism pathways, cellular proliferation, induction of apoptosis and cell
signalling in human breast cancer cells. Our results show that C75 and EGCG had
comparable effects in blocking FASN activity. Treating cancer cells with EGCG or
C75 induced apoptosis and caused a decrease in the active forms of oncoprotein
HER2, AKT and ERK1/2 to a similar degree. We observed, in contrast, marked
differential effects between C75 and EGCG on the fatty acid oxidation pathway.
While EGCG had either no effect or a moderate reduction in CPT-I activity, C75
stimulated CPT-I activity (up to 129%), even in presence of inhibitory levels of
malonyl-CoA, a potent inhibitor of the CPT-I enzyme. Taken together, these
findings indicate that pharmacological inhibition of FASN occurs uncoupled from
the stimulation of CPT-I with EGCG but not with C75, suggesting that EGCG might
be free of the CPT-I related in vivo weight-loss that has been associated with
C75. Our results establish EGCG as a potent and specific inhibitor of fatty acid
synthesis (FASN), which may hold promise as a target-directed anti-cancer drug.
PMID: 17902053 [PubMed - as supplied by publisher]
2: Breast Cancer Res Treat. 2007 Sep 28; [Epub ahead of print]
The prognostic significance of steroid receptor co-regulators in breast cancer:
co-repressor NCOR2/SMRT is an independent indicator of poor outcome.
Green AR, Burney C, Granger CJ, Paish EC, El-Sheikh S, Rakha EA, Powe DG,
Macmillan RD, Ellis IO, Stylianou E.
Division of Pathology, School of Molecular Medical Sciences, Nottingham
University Hospitals NHS and University of Nottingham, Nottingham, UK,
andrew.green@nottingham.ac.uk.
BACKGROUND: Advances in understanding the molecular basis of breast cancer has
necessitated a definition of improved indicators of prognosis that are central
to the underlying cancer biology and that reflect the heterogeneous nature of
the disease. This study investigates the pattern of expression of the steroid
receptor co-regulators NCOA1/SRC1, NCOA3/RAC3, NCOR2/SMRT, and CBP/p300 in
breast cancer. The aims were to identify whether their expression was related to
patient outcome, their relationships to known prognostic factors and to provide
a basis for further research into the mechanistic significance of such
associations. METHODS: The protein levels of steroid receptor co-regulators were
assessed by immunohistochemistry in a large well-characterised series of breast
carcinomas prepared as tissue microarrays. Relationships between these targets,
other clinicopathological variables and patients' outcome were examined.
RESULTS: NCOR2/SMRT was an independent prognostic indicator of overall patient
survival (OS) and disease free interval (DFI) and was significantly correlated
with distant metastases and local recurrence whereas tumours expressing
NCOA1/SRC1 had a significantly longer OS and DFI. There were also significant
correlations between co-regulator expression of NCOA1/SRC1, CBP/p300 and
NCOA3/RAC3, which were associated with lower tumour grade. NCOA1/SRC1 was also
correlated with smaller tumour size. Furthermore, the co-activators had a
significant association with steroid receptors, particularly ERalpha.
CONCLUSIONS: NCOR2/SMRT is associated with poor patient outcome, independent of
other prognostic factors. In contrast, steroid receptor co-activator expression
is generally associated with a good prognosis. Further investigations are needed
to establish the mechanisms of these links between the steroid receptor
co-regulator system and patient outcome.
PMID: 17902051 [PubMed - as supplied by publisher]
3: Breast Cancer Res Treat. 2007 Sep 27; [Epub ahead of print]
Old masters as clinical photographers: multifocal breast cancer diagnosed 400
years ago.
Grau JJ, Estrach T.
Oncology Department, Corporacio Sanitaria Clinic, University of Barcelona,
Villarroel, Barcelona, 170-08036, Spain, jjgrau@clinic.ub.es.
It is common belief among physicians the idea that breast cancer was not
diagnosed centuries ago. Nevertheless, there are reports suggesting that old
masters and even common people knew this dramatic disease. In the 16th and 17th
centuries, famous artists painted things exactly as they saw them. This allows
the detection of breast tumours, as have been previously published. We have
discovered a new case of breast cancer in an engraving after Titian's painting.
The woman in the painting shows two tumour masses in her right breast, with skin
and nipple retraction to the homo lateral axila, suggesting a multifocal breast
cancer. Other diagnostic options, such as breast tuberculosis or Mondor's
disease, have to be established. The findings suggest that this is the first
imaging report of a multifocal breast cancer. Old masters acted, in fact, as
clinical photographers.
PMID: 17902050 [PubMed - as supplied by publisher]
4: Breast Cancer Res Treat. 2007 Sep 28; [Epub ahead of print]
Insulin receptor substrate-1 involvement in epidermal growth factor receptor and
insulin-like growth factor receptor signalling: implication for Gefitinib
('Iressa') response and resistance.
Knowlden JM, Jones HE, Barrow D, Gee JM, Nicholson RI, Hutcheson IR.
Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff
University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3XF, UK,
hutchesonir@cf.ac.uk.
Classically the insulin receptor substrate-1 (IRS-1) is an essential component
of insulin-like growth factor type 1 receptor (IGF-IR) signalling, providing an
interface between the receptor and key downstream signalling cascades. Here,
however, we show that in tamoxifen-resistant MCF-7 (Tam-R) breast cancer cells,
that are highly dependent on epidermal growth factor receptor (EGFR) for growth,
IRS-1 can interact with EGFR and be preferentially phosphorylated on tyrosine
(Y) 896, a Grb2 binding site. Indeed, phosphorylation of this site is greatly
enhanced by exposure of these cells, and other EGFR-positive cell lines, to EGF.
Importantly, while IGF-II promotes phosphorylation of IRS-1 on Y612, a PI3-K
recruitment site, it has limited effect on Y896 phosphorylation in Tam-R cells.
Furthermore, EGF and IGF-II co-treatment, reduces the ability of IGF-II to
phosphorylate Y612, whilst maintaining Y896 phosphorylation, suggesting that the
EGFR is the dominant recruiter of IRS-1 in this cell line. Significantly,
challenge of Tam-R cells with the EGFR-selective tyrosine kinase inhibitor
gefitinib, for 7 days, reduces IRS-1/EGFR association and IRS-1 Y896
phosphorylation, while promoting IRS-1/IGF-IR association and IRS-1 Y612
phosphorylation. Furthermore, gefitinib significantly enhances IGF-II-mediated
phosphorylation of IRS-1 Y612 and AKT in Tam-R cells. Importantly, induction of
this pathway by gefitinib can be abrogated by inhibition/downregulation of the
IGF-IR. Our data would therefore suggest a novel association exists between the
EGFR and IRS-1 in several EGFR-positive cancer cell lines. This association acts
to promote phosphorylation of IRS-1 at Y896 and drive MAPK signalling whilst
preventing recruitment of IRS-1 by the IGF-IR and inhibiting signalling via this
receptor. Treatment with gefitinib alters the dynamics of this system, promoting
IGF-IR signalling, the dominant gefitinib-resistant growth regulatory pathway in
Tam-R cells, thus, potentially limiting its efficacy.
PMID: 17902048 [PubMed - as supplied by publisher]
5: Breast Cancer Res Treat. 2007 Sep 28; [Epub ahead of print]
MAZ drives tumor-specific expression of PPAR gamma 1 in breast cancer cells.
Wang X, Southard RC, Allred CD, Talbert DR, Wilson ME, Kilgore MW.
Department of Molecular and Biomedical Pharmacology, University of Kentucky
College of Medicine, MS 305, Chandler Medical Center 800 Rose Street, Lexington,
KY, 40536-0298, USA, M.Kilgore@uky.edu.
The peroxisome proliferator-activated receptor gamma 1 (PPARgamma1) is a nuclear
receptor that plays a pivotal role in breast cancer and is highly over-expressed
relative to normal epithelia. We have previously reported that the expression of
PPARgamma1 is mediated by at least six distinct promoters and expression in
breast cancer is driven by a tumor-specific promoter (pA1). Deletional analysis
of this promoter fragment revealed that the GC-rich, 263 bp sequence proximal to
the start of exon A1, is sufficient to drive expression in breast cancer cells
but not in normal, human mammary epithelial cells (HMEC). By combining the
disparate technologies of microarray and computer-based transcription factor
binding site analyses on this promoter sequence the myc-associated zinc finger
protein (MAZ) was identified as a candidate transcription factor mediating
tumor-specific expression. Western blot analysis and chromatin
immunoprecipitation assays verify that MAZ is overexpressed in MCF-7 cells and
is capable of binding to the 263 bp promoter fragment, respectively.
Furthermore, the over-expression of MAZ in HMEC is sufficient to drive the
expression of PPARgamma1 and does so by recruiting the tumor-specific promoter.
This results in an increase in the amount of PPARgamma1 capable of binding to
its DNA response element. These findings help to define the molecular mechanism
driving the high expression of PPARgamma1 in breast cancer and raise new
questions regarding the role of MAZ in cancer progression.
PMID: 17902047 [PubMed - as supplied by publisher]