Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005 Apr 10;23(11):2469-76.
doi: 10.1200/JCO.2005.01.172. Epub 2005 Mar 7.

Molecular changes in tamoxifen-resistant breast cancer: relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase

Affiliations

Molecular changes in tamoxifen-resistant breast cancer: relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase

M Carolina Gutierrez et al. J Clin Oncol. .

Abstract

Purpose: To evaluate growth factor receptor cross talk with the estrogen receptor (ER) in paired clinical breast cancer specimens and in a xenograft model before tamoxifen and at tumor progression as a possible mechanism for tamoxifen resistance.

Methods: Specimen pairs from 39 patients were tissue arrayed and stained for ER, progesterone receptor (PgR), Bcl-2, c-ErbB2 (HER-2), and phosphorylated (p) p38 mitogen-activated protein kinase (MAPK), p-ERK1/2 MAPK, and p-Akt. Xenograft MCF-7 tumors before and after tamoxifen resistance were assessed for levels of p-p38.

Results: Pretreatment, there were strong correlations between ER, PgR, and Bcl-2, and an inverse correlation between ER and HER-2. These correlations were lost in the tamoxifen- resistant tumors and replaced by strong correlations between ER and p-p38 and p-ERK. ER expression was lost in 17% of resistant tumors. Three (11%) of the 26 tumors originally negative for HER-2 became amplified and/or overexpressed at resistance. All ER-positive tumors that overexpressed HER-2 originally or at resistance expressed high levels of p-p38. In the pretreatment and tamoxifen-resistant specimens, there were strong correlations between p-p38 and p-ERK. In the tamoxifen-resistant xenograft tumors, like the clinical samples, there was a striking increase in p-p38.

Conclusion: The molecular pathways driving tumor growth can change as the tumor progresses. Crosstalk between ER, HER-2, p38, and ERK may contribute to tamoxifen resistance and may provide molecular targets to overcome this resistance.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms