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BMC Cancer

, 9:19

First Online: 14 January 2009Received: 27 March 2008Accepted: 14 January 2009DOI: 10.1186-1471-2407-9-19

Cite this article as: Cotroneo, M.S., Haag, J.D., Stapel, N.R. et al. BMC Cancer 2009 9: 19. doi:10.1186-1471-2407-9-19


BackgroundInflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund-s adjuvant FA promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene.

MethodsThe effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed.

ResultsRats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis.

ConclusionOur data suggests that systemic inflammation induced by Freund-s adjuvant FA promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer.

AbbreviationsFAFreund-s adjuvant

IACUCInstitutional Animal Care and Use Committee


CFAFreund-s complete adjuvant

IFAFreund-s incomplete adjuvant

PBSphosphate buffered saline

NIHNational Institutes of Health

ABCavidin: biotinylated enzyme complex


TEBterminal end buds

TdTterminal deoxynucleotidyl transferase

ANOVAanalysis of variance

DCISductal carcinoma in situ

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-19 contains supplementary material, which is available to authorized users.

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Autor: Michelle S Cotroneo - Jill D Haag - Nicholas R Stapel - Jordy L Waller - Stephan Woditschka - Michael N Gould


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