Haploid Inactivation of the Amplified-in-Breast Cancer 3 Coactivator Reduces the Inhibitory Effect of Peroxisome Proliferator-Activated Receptor γ and Retinoid X Receptor on Cell Proliferation and Accelerates Polyoma Middle-T Antigen-Induced Mammary Tumorigenesis in Mice

Zhang, Hao; Kuang, Shao Qing; Liao, Lan; Zhou, Suoling; Xu, Jianming

doi:10.1158/0008-5472.can-04-1176

Cited by 26 publications

(31 citation statements)

References 53 publications

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“…For example, a recent study suggests that the coactivator amplified-in-breast cancer 3 is needed for the (21). Studies from our own group also indicate that responsiveness to rosiglitazone requires at least one functional PTEN allele such that tumors with homozygous PTEN deletions or promoter mutations would prove refractory to treatment (22).…”

Section: Discussionmentioning

confidence: 93%

Pilot Study of Rosiglitazone Therapy in Women with Breast Cancer: Effects of Short-term Therapy on Tumor Tissue and Serum Markers

Yee¹,

Williams²,

Wen³

et al. 2007

Clinical Cancer Research

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Purpose: Peroxisome proliferator-activated receptor g (PPARg) is a steroid nuclear receptor that is activated by natural compounds such as specific fatty acids and synthetic drugs such as thiazolidinedione antidiabetic agents. Expressed in normal and malignant mammary epithelial cells, activation of PPARg is associated with antiproliferative effects on human breast cancer cells in preclinical studies. The purpose of this study was to test the hypothesis that PPARg ligand therapy might inhibit tumor growth and progression in human breast cancer. Experimental Design: We conducted a pilot trial of short-term (2-6 weeks) treatment with the thiazolidinedione rosiglitazone in 38 women with early-stage (T is -T 2 , N 0-1 , M 0 ) breast cancer, administered between the time of diagnostic biopsy and definitive surgery. Results: Short-term treatment with rosiglitazone (8 mg/d) did not elicit significant effects on breast tumor cell proliferation using Ki67 expression as a measure of cell proliferation and surrogate marker of tumor growth and progression. In pretreatment tumors notable for nuclear expression of PPARg by immunohistochemistry, down-regulation of nuclear PPARg expression occurred following rosiglitazone administration (P = 0.005). No PPARG mutations were identified, and the incidence of P12A and H446H polymorphisms did not differ relative to U.S. controls (P = 0.5). Treatment with rosiglitazone resulted in increased serum adiponectin (P < 0.001), decreased insulin levels (P = 0.005), and increased insulin sensitivity (P = 0.004). Rosiglitazone was well tolerated without serious adverse events. Conclusion: Our data indicate that short-term rosiglitazone therapy in early-stage breast cancer patients leads to local and systemic effects on PPARg signaling that may be relevant to breast cancer.

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Section: Discussionmentioning

confidence: 93%

Pilot Study of Rosiglitazone Therapy in Women with Breast Cancer: Effects of Short-term Therapy on Tumor Tissue and Serum Markers

Yee¹,

Williams²,

Wen³

et al. 2007

Clinical Cancer Research

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“…First, in an interesting study carried out in mouse models (31), haploid inactivation of ASC-2 was found to accelerate polyoma middle-T antigen-induced mammary tumorigenesis. Second, PTIP, which has been proposed to play important roles in cellular responses to DNA damage (32,33), recently was identified as an additional component of ASCOM (9,10).…”

Section: Targeted Inactivation Of Mll3 H3k4 Methyltransferase Activitmentioning

confidence: 99%

A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4

Lee

Kim

Lee

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

192

193

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ASC-2, a multifunctional coactivator, forms a steady-state complex, named ASCOM (for ASC-2 COMplex), that contains the histone H3-lysine-4 (H3K4)-methyltransferase MLL3 or its paralogue MLL4. Somewhat surprisingly, given prior indications of redundancy between MLL3 and MLL4, targeted inactivation of the MLL3 H3K4-methylation activity in mice is found to result in ureter epithelial tumors. Interestingly, this phenotype is exacerbated in a p53 ؉/؊ background and the tumorigenic cells are heavily immunostained for ␥H2AX, indicating a contribution of MLL3 to the DNA damage response pathway through p53. Consistent with the in vivo observations, and the demonstration of a direct interaction between p53 and ASCOM, cell-based assays have revealed that ASCOM, through ASC-2 and MLL3/4, acts as a p53 coactivator and is required for H3K4-trimethyation and expression of endogenous p53-target genes in response to the DNA damaging agent doxorubicin. In support of redundant functions for MLL3 and MLL4 for some events, siRNA-mediated down-regulation of both MLL3 and MLL4 is required to suppress doxorubicin-inducible expression of several p53-target genes. Importantly, this study identifies a specific H3K4 methytransferase complex, ASCOM, as a physiologically relevant coactivator for p53 and implicates ASCOM in the p53 tumor suppression pathway in vivo.

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“…The WT/PyMT and SRC-1 Ϫ/Ϫ /PyMT mammary tumor tissues (Ϸ1 mm 3 in size) were sliced from primary tumors of different donor mice and reciprocally implanted into the mammary fat pads of 8-to 12-weekold female SRC-1 Ϫ/Ϫ and WT recipient mice as described (8,35). Tumor growth was monitored once a week.…”

Section: Examination Of Lung Metastasismentioning

confidence: 99%

“…Expression of the MMTV-PyMT transgene in mice causes rapid formation of mammary carcinomas with all identifiable stages similar to human breast cancer progression (33). Extensive lung metastasis also develops in all MMTV-PyMT mice (8,(33)(34)(35), which makes the animal model ideal for investigating the role of SRC-1 in breast cancer metastasis. Furthermore, biological markers expressed in PyMT-induced mammary tumors are consistent with those expressed in human breast cancers.…”

mentioning

confidence: 99%

“…Furthermore, biological markers expressed in PyMT-induced mammary tumors are consistent with those expressed in human breast cancers. For instance, the loss of ER␣, PR, and integrin-␤1 and the persistent expression of HER2 and cyclin D1 were observed in PyMT-induced tumors as they progressed to the malignant stage (35,36). By inducing and characterizing the initiation and progression of mammary tumors in WT/PyMT and SRC-1 Ϫ/Ϫ /PyMT mice, we have substantiated the role of SRC-1 in mammary cancer metastasis and uncovered molecular pathways responsible for SRC-1 to promote metastasis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation

Wang

Yuan

Liao

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

119

127

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Haploid Inactivation of the Amplified-in-Breast Cancer 3 Coactivator Reduces the Inhibitory Effect of Peroxisome Proliferator-Activated Receptor γ and Retinoid X Receptor on Cell Proliferation and Accelerates Polyoma Middle-T Antigen-Induced Mammary Tumorigenesis in Mice

Cited by 26 publications

References 53 publications

Pilot Study of Rosiglitazone Therapy in Women with Breast Cancer: Effects of Short-term Therapy on Tumor Tissue and Serum Markers

Pilot Study of Rosiglitazone Therapy in Women with Breast Cancer: Effects of Short-term Therapy on Tumor Tissue and Serum Markers

A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4

Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation

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