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Media type:
E-Article
Title:
TGF‐Beta Signaling in Breast Cancer
Contributor:
BUCK, MIRIAM B.;
KNABBE, CORNELIUS
Published:
Wiley, 2006
Published in:
Annals of the New York Academy of Sciences, 1089 (2006) 1, Seite 119-126
Language:
English
DOI:
10.1196/annals.1386.024
ISSN:
0077-8923;
1749-6632
Origination:
Footnote:
Description:
<jats:p><jats:bold><jats:sc>Abstract: </jats:sc></jats:bold> <jats:bold>The antiestrogen tamoxifen is one of the most successful drugs in the endocrine treatment of breast cancer and significantly reduces the risk of recurrence and death. Antiestrogens act by inhibiting the production of growth‐stimulatory factors as well as by activating peptides with growth‐inhibitory effects like transforming growth factor‐ beta (TGF‐β). In hormone‐responsive breast cancer cells treatment with antiestrogens leads to the conversion of TGF‐β1 into a biologically active form. Expression of TGF‐β2 and TGF‐β receptor (TβR) II is induced via a transcriptional mechanism involving p38 MAP kinase. Inhibition of p38 abolishes antiestrogen‐dependent growth inhibition. However, the role of TGF‐β in breast cancer progression is ambiguous, as it was shown to display both tumor‐suppressing and ‐enhancing effects. A polymorphism in the promoter of TGF‐β2 that enhances expression of the protein was associated with lymph node metastasis in breast cancer patients, pointing to a role of TGF‐β2 in the process of invasion. An immunohistochemical study on TβRI and TβRII expression in breast cancer tissues indicates that the estrogen receptor (ER) status of a tumor is an important marker and a potential mediator of the transition of TGF‐β from tumor suppressor to tumor promoter. In ER‐negative tumors, expression of TβRII was associated with a subset of tumors that appeared to be highly aggressive, leading to strongly reduced overall survival times. Further characterization of the influence of ER expression on TGF‐β signal transduction shows that ER‐α plays a crucial role in TGF‐β signaling.</jats:bold> </jats:p>