Stabilization of cyclin D1 mRNA via the phosphatidylinositol 3-kinase pathway in MCF-7 human breast cancer cells

Treatment of quiescent MCF-7 human breast cancer cells with either the polypeptide growth factors insulin-like growth factor-I (IGF-I) or epidermal growth factor (EGF), the steroid hormone estradiol (E2) or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) results in increased steady-state levels of cyclin D1 mRNA and protein. Unexpectedly, this elevation of cyclin D1 expression by all of these agents is inhibited by the specific phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002. Since transcriptional activation of the cyclin D1 promoter by EGF, E2 and TPA is independent of PI3-K activity, these findings suggest a post-transcriptional role for PI3-K in the regulation of cyclin D1 expression. Here we show that inhibition of PI3-K by LY294002 decreases the half-life of the 4.5 kb cyclin D1 mRNA species. In contrast, the stability of the 1.5 kb cyclin D1 mRNA is not affected by PI3-K inhibition. PI3-K-mediated stabilization of mRNA is not a general phenomenon, since other rapidly regulated and unstable mRNAs, such as those encoding c-fos, c-jun and c-myc, are not stabilized upon activation of the PI3-K signaling pathway.

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The Potentiation of Estrogen on Insulin-like Growth Factor I Action in MCF-7 Human Breast Cancer Cells Includes Cell Cycle Components

Journal of Biological Chemistry ◽

10.1074/jbc.m006741200 ◽

2000 ◽

Vol 275 (46) ◽

pp. 35893-35901 ◽

Cited By ~ 100

Author(s):

Joelle Dupont ◽

Michael Karas ◽

Derek LeRoith

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Growth Factor ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Factor I ◽

Mcf 7

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Vitamin D Induced Up-Regulation of Keratinocyte Growth Factor (FGF-7/KGF) in MCF-7 Human Breast Cancer Cells

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.2000.2998 ◽

2000 ◽

Vol 273 (2) ◽

pp. 675-680 ◽

Cited By ~ 20

Author(s):

Alex Lyakhovich ◽

Nickolai Aksenov ◽

Pasi Pennanen ◽

Susanna Miettinen ◽

Merja H. Ahonen ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Growth Factor ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Keratinocyte Growth Factor ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mcf 7

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Analogs of GnRH-I and GnRH-II inhibit epidermal growth factor-induced signal transduction and resensitize resistant human breast cancer cells to 4OH-tamoxifen

Acta Endocrinologica ◽

10.1530/eje.1.01996 ◽

2005 ◽

Vol 153 (4) ◽

pp. 613-625 ◽

Cited By ~ 20

Author(s):

Andreas R Günthert ◽

Carsten Gründker ◽

Agnes Olota ◽

Julia Läsche ◽

Nicola Eicke ◽

...

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Antiproliferative Effects ◽

Epidermal Growth ◽

Mcf 7

About 50–64% of human breast cancers express receptors for GnRH-I. Direct antiproliferative effects of analogs of GnRH-I on human breast cancer cell lines have been shown. They are at least in part mediated by antagonizing growth promoting effects of estradiol, epidermal growth factor (EGF) or insulin-like growth factor. Recently, expression of a putative receptor for GnRH-II in human tissues was demonstrated. Antiproliferative effects of GnRH-II in human endometrial and ovarian cancer cells were shown not to be mediated through the GnRH-I receptor. Now we demonstrate direct anti-proliferative effects of the GnRH-I analog Triptorelin and the GnRH-II analog [d-Lys6]GnRH-II in MCF-7 and T47D human breast cancer cells expressing GnRH-I receptors and putative GnRH-II receptors. Pretreatment with Triptorelin or [d-Lys6]GnRH-II blocked EGF-induced autophosphoryla-tion of EGF receptor and activation of mitogen-activated protein kinase (extracellular-signal-regulated kinase 1/2 (ERK1/2)) in these cells. In sublines of MCF-7 and T47D cells, which were developed to be resistant to 4OH-tamoxifen, HER-2/p185 was overexpressed. Pretreatment of these cell lines with Triptorelin or [d-Lys6]GnRH-II completely abolished resistance to 4OH-tamoxifen, assessed by 4OH-tamoxifen-induced apoptosis. Analogs of GnRH-I and GnRH-II counteract EGF-dependent signal transduction in human breast cancer cells with expression of receptors for GnRH-I and GnRH-II. Through this mechanism, they probably reverse acquired resistance to 4OH-tamoxifen mediated through overexpression or activation of receptors of the c-erbB family.

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Proapoptotic and Antiproliferative Effects ofThymus caramanicuson Human Breast Cancer Cell Line (MCF-7) and Its Interaction with Anticancer Drug Vincristine

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/893247 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Saeed Esmaeili-Mahani ◽

Farzaneh Falahi ◽

Mohammad Mehdi Yaghoobi

Keyword(s):

Breast Cancer ◽

Cyclin D1 ◽

Cancer Cells ◽

Anticancer Drug ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Caspase 3 ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mcf 7

Thymus caramanicus Jalasis one of the species of thymus that grows in the wild in different regions of Iran. Traditionally, leaves of this plant are used in the treatment of diabetes, arthritis, and cancerous situation. Therefore, the present study was designed to investigate the selective cytotoxic and antiproliferative properties ofThymus caramanicusextract (TCE). MCF-7 human breast cancer cells were used in this study. Cytotoxicity of the extract was determined using MTT and neutral red assays. Biochemical markers of apoptosis (caspase 3, Bax, and Bcl-2) and cell proliferation (cyclin D1) were evaluated by immunoblotting. Vincristine was used as anticancer control drug in extract combination therapy. The data showed that incubation of cells with TCE (200 and 250 μg/mL) significantly increased cell damage, activated caspase 3 and Bax/Bcl2 ratio. In addition, cyclin D1 was significantly decreased in TCE-treated cells. Furthermore, concomitant treatment of cells with extract and anticancer drug produced a significant cytotoxic effect as compared to extract or drugs alone. In conclusion, thymus extract has a potential proapoptotic/antiproliferative property against human breast cancer cells and its combination with chemotherapeutic agent vincristine may induce cell death effectively and be a potent modality to treat this type of cancer.

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