Proto-oncogene ACTR/AIB1 promotes cancer cell invasion by up-regulating specific matrix metalloproteinase expression

Li, Li B.; Louie, Maggie C.; Chen, Hongwu; Zou, June X.

doi:10.1016/j.canlet.2007.11.013

Cited by 36 publications

(28 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we cannot conclude from this study due to the low number of subjects in the treatment arms, we did observe a trend in which mRNA levels of SRC-3/AIB1 were higher in the groups with poor clinical outcome and unfavorable prognostic factors. This fits well with the role of SRC-3/AIB1 as an oncogene, in which the coactivator has been shown to directly regulate the expression of cell cycle regulators such as cyclin D1 (6,50), and also facilitate migration and the metastatic behavior of cells, in part through the transcriptional regulation of matrix metalloproteinases and the activation of the PI3K/Akt/mammalian target of rapamycin pathway (11)(12)(13).…”

Section: Discussionsupporting

confidence: 81%

“…Overexpression of SRC-3/ AIB1 increases the agonist properties of tamoxifen (9) and tamoxifen resistance develops when SRC-3/AIB1 is high and the transcriptional repressor paired box 2 (PAX2) is low in breast cancer cells (10). SRC-3/AIB1 is considered as an oncogene leading to mammary hypertrophy, hyperplasia, and breast cancer development (11)(12)(13). Overexpression of SRC-3/AIB1 has been found in 31% to 64% of human breast tumors and gene amplification in 2% to 10% (14)(15)(16)(17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of Low-Dose Tamoxifen on Steroid Receptor Coactivator 3/Amplified in Breast Cancer 1 in Normal and Malignant Human Breast Tissue

Moi

Flågeng

Gandini

et al. 2010

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Nuclear receptor coactivator expression and activity may partly explain the complex agonist/ antagonist effects of tamoxifen at clinical level. In a preoperative trial, dose reduction from 20 to 1 mg tamoxifen was associated with retained antiproliferative effect on breast cancer. Here, we assessed the gene expression of the steroid receptor coactivators SRC-1, SRC-2/transcription intermediary factor 2, and SRC-3/amplified in breast cancer 1 (AIB1) and the growth factor receptor HER-2/neu under three tamoxifen dose regimens.Experimental Design: Surgical specimens from estrogen receptor-positive breast cancer and adjacent normal breast tissue from 64 patients treated 4 weeks preoperatively with 20, 5, or 1 mg/d tamoxifen and 28 nontreated breast cancer controls were analyzed for coactivator and HER-2/neu mRNA expression using real-time reverse transcription-PCR. The gene expression levels were related to immunohistochemical expression of Ki67, serum levels of insulin-like growth factor I and sex hormone binding globulin, other prognostic factors, and clinical outcome.

show abstract

Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

Effect of Low-Dose Tamoxifen on Steroid Receptor Coactivator 3/Amplified in Breast Cancer 1 in Normal and Malignant Human Breast Tissue

Moi

Flågeng

Gandini

et al. 2010

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Molecular analyses indicated that resistant cells expressed higher levels of the cell cycle regulators cyclin E1, cdk2, and E2F1, all of which have been implicated in cancer progression (6)(7)(8)(9)(10)(11)(12)(13). We further showed that tamoxifen enhances the ERα/Sp-1 interaction and promotes the recruitment of ERα and Sp-1 to the proximal promoter of E2F1 in MCF7TamR cells.…”

Section: Introductionmentioning

confidence: 61%

Estrogen Receptor Regulates E2F1 Expression to Mediate Tamoxifen Resistance

Louie

McClellan

Siewit

et al. 2010

Molecular Cancer Research

Self Cite

View full text Add to dashboard Cite

Antiestrogen resistance often develops with prolonged exposure to hormone therapies, including tamoxifen, and is a major problem in the treatment of breast cancer. Understanding the mechanisms involved in the development of antiestrogen resistance is an important step in the development of new targeted therapies. Two forms of antiestrogen resistance exist: de novo resistance and acquired resistance. To mimic acquired resistance, we have established a tamoxifen-resistant breast cancer cell line (MCF-7TamR) by treating parental MCF-7 cells with tamoxifen over a period of 6 months to select for cells with the resistant phenotype. Characterization of the MCF-7TamR cells under normal, hormone-deprived, and tamoxifen-treated conditions suggests that these cells continue to grow in the presence of tamoxifen. Additionally, a greater percentage of resistant cells enter the S phase under tamoxifen conditions, compared with parental MCF-7 cells. Consistent with these growth results, molecular analysis indicates that tamoxifen-resistant cells express higher levels of cyclin E1, cdk2, ACTR, and E2F1. Faslodex or ICI 182, 780 (ICI)-mediated degradation of estrogen receptor (ER) reduced the proliferation of these cells, as well as the level of E2F1 expression in tamoxifen-resistant cells, suggesting that tamoxifen resistance and E2F1 expression are in part dependent on ER. We further showed that tamoxifen enhances the ERα/Sp-1 interaction and promotes the recruitment of ERα and Sp-1 to the proximal promoter of E2F1 in resistant cells. Collectively, our findings suggest that tamoxifen resistance is a result of increased ERα/Sp-1 interaction, which enhances the expression of E2F1 to promote tamoxifen resistance. Mol Cancer Res; 8(3); 343-52. ©2010 AACR.

show abstract

“…Interestingly, the SRC-3 gene promotes not only cell proliferation and transformation but also cancer cell migration and invasion (17,18). In cultured cells, SRC-3 promotes cancer cell invasion by coactivating PEA3- and AP-1-regulated MMP expression (19)(20)(21), but the invasive signals to SRC-3 are completely unknown. SRC-3 is phosphorylated at multiple residues upon the stimulation of growth factors or hormones (22)(23)(24).…”

mentioning

confidence: 99%

ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion

et al. 2012

View full text Add to dashboard Cite

In contrast to the well-studied classic MAPKs, such as ERK1/2, little is known concerning the regulation and substrates of the atypical MAPK ERK3 signaling cascade and its function in cancer progression. Here, we report that ERK3 interacted with and phosphorylated steroid receptor coactivator 3 (SRC-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (S857). This ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity in lung cancer cells. Importantly, knockdown of ERK3 or SRC-3 inhibited the ability of lung cancer cells to invade and form tumors in the lung in a xenograft mouse model. In addition, ERK3 was found to be highly upregulated in human lung carcinomas. Our study identifies a previously unknown role for ERK3 in promoting lung cancer cell invasiveness by phosphorylating SRC-3 and regulating SRC-3 proinvasive activity by site-specific phosphorylation. As such, ERK3 protein kinase may be an attractive target for therapeutic treatment of invasive lung cancer.

show abstract

Proto-oncogene ACTR/AIB1 promotes cancer cell invasion by up-regulating specific matrix metalloproteinase expression

Cited by 36 publications

References 46 publications

Effect of Low-Dose Tamoxifen on Steroid Receptor Coactivator 3/Amplified in Breast Cancer 1 in Normal and Malignant Human Breast Tissue

Effect of Low-Dose Tamoxifen on Steroid Receptor Coactivator 3/Amplified in Breast Cancer 1 in Normal and Malignant Human Breast Tissue

Estrogen Receptor Regulates E2F1 Expression to Mediate Tamoxifen Resistance

ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion

Contact Info

Product

Resources

About