Bcl-2 induces cyclin D1 promoter activity in human breast epithelial cells independent of cell anchorage

Lin, Han Yu; Lee, Y. J.; Li, G.; Pestell, Richard G.; Kim, H. R C

doi:10.1038/sj.cdd.4400770

Cited by 30 publications

(27 citation statements)

References 35 publications

(39 reference statements)

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“…When Bcl-2 was overexpressed in a human breast epithelial cell line, MCF10A, it caused an increase in the expression of cyclin D1. Bcl-2 was also found to be able to increase the activity of cyclin D1 promoter in both MCF10A and MCF-7 cells independent of anchorage conditions (42). The effects of both the loss of Bcl-2 and AIB1 could therefore contribute to greater reduction in cyclin D1 levels.…”

Section: Discussionmentioning

confidence: 85%

The Nuclear Receptor Coactivator AIB1 Mediates Insulin-like Growth Factor I-induced Phenotypic Changes in Human Breast Cancer Cells

Oh¹,

List²,

Reiter³

et al. 2004

Cancer Research

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The nuclear receptor coactivator AIB1 (amplified in breast cancer 1) is overexpressed in human breast cancers and is required for estrogen signaling. However, the role of AIB1 in breast cancer etiology is not known. Here, we show that AIB1 is rate-limiting for insulin-like growth factor I (IGF-I)-dependent phenotypic changes and gene expression in human breast cancer cells. Reduction of endogenous AIB1 levels by small interfering RNA in MCF-7 breast cancer cells prevented IGF-I-stimulated anchorage-independent growth by reducing IGF-I-dependent antianoikis. cDNA array and immunoblot analysis of gene expression revealed that reduction in AIB1 levels led to a significant decrease in the expression of several genes controlling the cell cycle and apoptosis. These AIB1-dependent changes were also observed in the presence of estrogen antagonist and were corroborated in the estrogen receptor-negative cell line MDA MB-231. AIB1 reduction decreased the expression of the IGF-I receptor and IRS-1 in MCF-7 but not in MDA MB-231 cells. IGF-Istimulated activation of AKT was reduced by AIB1 small interfering RNA treatment, whereas mitogen-activated protein kinase (extracellular signalregulated kinase 1/2) activation by IGF-I was unaffected. We conclude that AIB1 is required for IGF-I-induced proliferation, signaling, cell survival, and gene expression in human breast cancer cells, independent of its role in estrogen receptor signaling.

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Section: Discussionmentioning

confidence: 85%

The Nuclear Receptor Coactivator AIB1 Mediates Insulin-like Growth Factor I-induced Phenotypic Changes in Human Breast Cancer Cells

Oh¹,

List²,

Reiter³

et al. 2004

Cancer Research

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“…However, some studies suggest that cyclin-D1 may have antitumor effects. Turner et al 37 suggested that high expression of cyclin-D1 can make the tumor more sensitive to radiation, while Lin et al 38 suggested that cyclin-D1 may lead to induction of apoptosis, cellular senescence and cellular growth inhibition. In our study we did not find a correlation between cyclin-D1 expression and cell proliferation activity mirrored by Ki-67, which supports the interpretation that cyclin-D1 might demonstrate other functions that are not related to cell-cycle progression and tumor aggressiveness.…”

Section: Nuclear Egfr In Breast Cancermentioning

confidence: 99%

Nuclear EGFR in ductal invasive breast cancer: correlation with cyclin-D1 and prognosis

et al. 2010

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The epidermal growth factor receptor (EGFR)-family and cyclin-D1 have been extensively studied in breast cancer; however systematic studies that examine protein expression and gene status in the same cohort of patients are lacking. Also emerging evidences suggest existence of a direct EGFR-signaling pathway, which involves cellular transport of EGFR from cell membrane to the nucleus, and transcriptional regulation of the target genes. Thus, we examined the protein expression of membrane EGFR, nuclear EGFR, cyclin-D1 and the corresponding gene status in 113 breast carcinomas by immunohistochemistry and fluorescence in situ hybridization using tissue microarrays. Membrane EGFR overexpression and EGFR gene amplification were detected in 2% cases, while nuclear EGFR was detected in 40% of cases, with 12% having high nuclear EGFR staining. Nuclear EGFR correlated with tumor size (P ¼ 0.0005), lymph node metastasis (P ¼ 0.0288), Nottingham prognostic index (P ¼ 0.0011) and estrogen receptor (ER) expression (P ¼ 0.0258) but the letter correlation was observed only in premenopausal group of patients. Strong cyclin-D1 expression and cyclin-D1 gene (CCND1) amplification were found in 64 and 13% of the cases, respectively. Cyclin-D1 expression showed positive correlation with ER (P ¼ 0.0113) and inverse correlation with Nottingham prognostic index (P ¼ 0.0309) and membrane EGFR (P ¼ 0.0201). CCND1 amplification also showed inverse correlation with membrane EGFR (P ¼ 0.0420). A strong correlation between membrane EGFR expression and gene amplification (P ¼ 0.0035), as well as cyclin-D1 overexpression and gene amplification (P ¼ 0.0362), was demonstrated. On univariate analysis cyclin-D1 expression showed a correlation with longer overall survival in the premenopausal group and nuclear EGFR correlated with shorter overall survival in whole cohort as well in the premenopausal group of patients. Multivariate analysis revealed nuclear EGFR to be an independent prognostic factor and showed 3.4 times greater mortality risk for nuclear EGFR þ þ þ patients as compared with nuclear EGFR negative patients (hazard ratio ¼ 3.402; P ¼ 0.0026).

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“…67,[133][134][135][136] Furthermore, paxillin is able to promote cell survival signaling through its direct interaction with the pro-survival, proto-oncogene bcl -2, 20 which is known to function to prevent apoptosis in the absence of cell adhesion in both normal and cancerous cells, in part through maintaining adhesionrelated signaling through FAK. 137,138 Importantly, neither Hic-5 nor leupaxin interacts with bcl-2 family members, although the former may regulate cell survival by other mechanisms, for example, through regulating the nuclear function of the pro-survival protein cyclin D1. 139 Furthermore, Hic-5 interacts with the heat shock protein 27 (hsp27) to increase cell death in response to heat shock.…”

Section: Monographsmentioning

confidence: 99%

Diverse Roles for the Paxillin Family of Proteins in Cancer

Deakin¹,

Pignatelli²,

Turner

2012

Genes & Cancer

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The paxillin family of intracellular scaffold proteins includes paxillin, Hic-5, and leupaxin, and all have been identified as key regulators of the cellular migration machinery in both 2-and 3-dimensional microenvironments. Herein, we provide insight into the roles of these proteins during tumorigenesis and metastasis, highlighting their functions in cancer initiation as well as tumor cell dissemination and survival. Furthermore, we speculate on the potential of paxillin family proteins as both future prognostic and therapeutic targets.

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Bcl-2 induces cyclin D1 promoter activity in human breast epithelial cells independent of cell anchorage

Cited by 30 publications

References 35 publications

The Nuclear Receptor Coactivator AIB1 Mediates Insulin-like Growth Factor I-induced Phenotypic Changes in Human Breast Cancer Cells

The Nuclear Receptor Coactivator AIB1 Mediates Insulin-like Growth Factor I-induced Phenotypic Changes in Human Breast Cancer Cells

Nuclear EGFR in ductal invasive breast cancer: correlation with cyclin-D1 and prognosis

Diverse Roles for the Paxillin Family of Proteins in Cancer

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