High-Fat Corn Oil Promotes Mammary Adenocarcinomas While High Olive oil diet

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High-Fat Corn Oil Promotes Mammary Adenocarcinomas While High Olive

Oil Diet does not

JoAnn Guest

Jan 15, 2007 10:32 PST

 

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High-Fat Corn Oil Diet Promotes the Development of High Histologic

Grade Rat DMBA-Induced Mammary Adenocarcinomas, While High Olive Oil

Diet Does Not

 

http://www.annieappleseedproject.org/typofoilmato.html

 

Irmgard Costa Department of Cell Biology, Physiology and Immunology,

Physiology Unit, Medical School, Universitat Aut¨°noma de Barcelona,

Spain; Department of Pathology, Hospital General de Granollers,

Barcelona, Spain

 

Raquel Moral Department of Cell Biology, Physiology and Immunology,

Physiology Unit, Medical School, Universitat Aut¨°noma de Barcelona,

Spain

 

Montserrat Solanas Department of Cell Biology, Physiology and

Immunology, Physiology Unit, Medical School, Universitat Aut¨°noma

de

Barcelona, Spain

 

and Eduard Escrich Department of Cell Biology, Physiology and

Immunology, Physiology Unit, Medical School, Universitat Aut¨°noma

de

Barcelona, Spain

 

Abstract

 

Effects of a high corn oil and a high olive oil diet on the

histopathologic characteristics of rat

dimethylbenz(¦Á)anthracene-induced mammary adenocarcinomas were

investigated in comparison with those of a control low-fat diet.

 

Two experimental series (A and B) studied the influence of a high

corn

oil diet on the initiation and the promotion of mammary

carcinogenesis,

while another one © assessed the effects of the two dietary lipids

on

the promotion. Nine parameters have been analyzed and a new

histologic

grading method, adapted to rat tumors, has been applied in each

carcinoma.

 

High corn oil diets, particularly when acting as promoters,

associated

with higher-grade carcinomas than control (p < 0.05) and high olive

oil

groups. Stromal invasion and tumoral necrosis were more prominent

and a

prevailing cribriform pattern was observed (p < 0.05).

 

High olive oil diet adenocarcinomas exhibited a predominantly low

histologic grade and few necrotic and invasive areas, similar to the

control, and they presented the highest percentage of papillary

areas.

 

Lymphoplasmacytic and mast cell infiltration were also influenced by

the

dietary lipids. Thus, high corn oil diet adenocarcinomas presented a

higher degree of morphological malignancy than control and high

olive

oil tumors, which is in line with the greater clinical malignancy

described in rats from the former group and the non-promoting effect

of

the high olive oil diet.

 

As far as we are concerned, a similar histopathologic approach of

the

effects of the dietary lipids on experimental breast cancer has not

been

carried out up to now.

 

Export Citation: Text RIS doi:10.1023/B:BREA.0000036896.75548.0c

 

Breast Cancer Research and Treatment 86 (3): 225-235, August 2004

 

Article ID: 5271305

 

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Oleic acid, the main monounsaturated fatty acid of olive oil,

suppresses

Her-2/neu (erbB-2) expression and synergistically enhances the

growth

inhibitory effects of trastuzumab (HerceptinTM) in breast cancer

cells

with Her-2/neu oncogene amplification

 

J. A. Menendez1,2,*, L. Vellon1, R. Colomer3 and R. Lupu1,2,*

 

1 Department of Medicine, Breast Cancer Translational Research

Laboratory, Evanston Northwestern Healthcare Research Institute,

Evanston, IL; 2 Department of Medicine, Northwestern University

Feinberg

School of Medicine, Chicago, IL, USA; 3 Institut Catala d'Oncologia,

Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain

 

* Correspondence to: Dr J. A. Menendez or Ruth Lupu, Evanston

Northwestern Healthcare Research Institute, 1001 University Place,

Evanston, IL 60201, USA. Tel: +1-847-570-7672; Fax: +1-847-570-8022;

Email: jmene- orEmail: r-l-

 

Background: The relationship between the intake of olive oil, the

richest dietary source of the monounsaturated fatty acid oleic acid

(OA;

18:1n-9), and breast cancer risk and progression has become a

controversial issue.

 

Moreover, it has been suggested that the protective effects of olive

oil

against breast cancer may be due to some other components of the oil

rather than to a direct effect of OA.

 

Methods: Using flow cytometry, western blotting, immunofluorescence

microscopy, metabolic status (MTT), soft-agar colony formation,

enzymatic in situ labeling of apoptosis-induced DNA double-strand

breaks

(TUNEL assay analyses), and caspase-3-dependent poly-ADP ribose

polymerase (PARP) cleavage assays, we characterized the effects of

exogenous supplementation with OA on the expression of Her-2/neu

oncogene, which plays an active role in breast cancer etiology and

progression.

 

In addition, we investigated the effects of OA on the efficacy of

trastuzumab (HerceptinTM), a humanized monoclonal antibody binding

with

high affinity to the ectodomain of the Her-2/neu-coded p185Her-2/neu

oncoprotein. To study these issues we used BT-474 and SKBr-3 breast

cancer cells, which naturally exhibit amplification of the Her-2/neu

oncogene.

 

Results: Flow cytometric analyses demonstrated a dramatic (up to

46%)

reduction of cell surface-associated p185Her-2/neu following

treatment

of the Her-2/neu-overexpressors BT-474 and SK-Br3 with OA.

 

Indeed, this effect was comparable to that found following exposure

to

optimal concentrations of trastuzumab (up to 48% reduction with 20

µg/ml

trastuzumab).

 

Remarkably, the concurrent exposure to OA and suboptimal

concentrations

of trastuzumab (5 µg/ml) synergistically down-regulated Her-2/neu

expression, as determined by flow cytometry (up to 70% reduction),

immunoblotting, and immunofluorescence microscopy studies.

 

The nature of the cytotoxic interaction between OA and trastuzumab

revealed a strong synergism, as assessed by MTT-based cell viability

and

anchorage-independent soft-agar colony formation assays.

 

Moreover, OA co-exposure synergistically enhanced trastuzumab

efficacy

towards Her-2/neu overexpressors by promoting DNA fragmentation

associated with apoptotic cell death, as confirmed by TUNEL and

caspase-3-dependent PARP cleavage.

 

In addition, treatment with OA and trastuzumab dramatically

increased

both the expression and the nuclear accumulation of p27Kip1, a

cyclin-dependent kinase inhibitor playing a key role in the onset

and

progression of Her-2/neu-related breast cancer.

 

Finally, OA co-exposure significantly enhanced the ability of

trastuzumab to inhibit signaling pathways downstream of Her-2/neu,

including phosphoproteins such as AKT and MAPK.

 

Conclusions: These findings demonstrate that OA, the main

monounsaturated fatty acid of olive oil, suppresses Her-2/neu

overexpression, which, in turn, interacts synergistically with

anti-Her-2/neu immunotherapy by promoting apoptotic cell death of

breast

cancer cells with Her-2/neu oncogene amplification.

 

This previously unrecognized property of OA offers a novel molecular

mechanism by which individual fatty acids may regulate the malignant

behavior of breast cancer cells and therefore be helpful in the

design

of future epidemiological studies and, eventually, dietary

counseling.

 

Annals of Oncology Advance Access originally published online on

January

10, 2005 Annals of Oncology 2005 16(3):359-371;

doi:10.1093/annonc/mdi090

 

 

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www.geocities.com/mrsjoguest/Diets