In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1242-1242
Abstract:
The complex agonist/antagonist effects of tamoxifen may partly be explained by changes in nuclear receptor coactivator expression and activity. In addition, overexpression of the epidermal growth factor receptor HER-2/neu is associated with poor prognosis and tamoxifen resistance in conjunction with coactivator SRC-3/AIB1. In this study, 64 patients with ER positive breast cancer were randomly treated with 20, 5 or 1 mg tamoxifen/day for 4 week preoperatively. 28 ER positive patients were included as not-treated controls. Specimens at the time of surgery were collected from tumor tissue and normal breast tissue below 1 cm from the tumor. Real-time PCR analyses were performed to measure mRNA expression of the members of the steroid receptor coactivator (SRC) family; SRC-1, SRC-2/TIF-2, SRC-3/AIB1 and the receptor HER-2/neu. The mRNA levels were analyzed with the focus on effects of tamoxifen dose, tissue type, as well as potential correlation to the plasma levels of the biomarkers IGF-I, SHBG and immunohistochemical expression of Ki-67. The mRNA-levels of SRC-1, SRC-2/TIF-2, SRC-3/AIB1 and HER-2/neu were all significantly higher in tumors compared to normal tissue (P & lt; 0.001). Tamoxifen significantly increased mRNA expression level of the coactivators in a dose-independent manner in both tissue-types, with the clearest effect for SRC-3/AIB1 (P & lt; 0.001). There was no difference in HER-2/neu mRNA levels in tamoxifen treated samples compared to controls. We observed no significant correlation between mRNA levels of the coactivators and HER-2/neu with IGF-1, SHBG or Ki-67. In conclusion, nuclear receptor coactivators were significantly higher both in breast tumors and normal tissue after tamoxifen treatment; however there was no difference in mRNA levels between the tamoxifen doses of 1, 5 or 20 mg/day. Whether such an increase in expression of coactivators could be a sign of effective endocrine treatment or an attempt of the cells to shift back to a more estrogen sensitive state, remains to be elucidated. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1242.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-1242
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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