4-Hydroxyestradiol Induces Anchorage-Independent Growth of Human Mammary Epithelial Cells via Activation of IκB Kinase: Potential Role of Reactive Oxygen Species

Park, Sin-Aye; Na, Hye-Kyung; Kim, Eun‐Hee; Cha, Young‐Nam; Surh, Young‐Joon

doi:10.1158/0008-5472.can-08-2177

Cited by 76 publications

(76 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ROS toxicity and its involvement in different human pathologies underline the need to identify new pathways and proteins that can mitigate the adverse effects of ROS accumulation (16,(33)(34)(35)(36)(37). It is surprising that, despite the widely assumed involvement of ROS in DNA damage in plants, no transcriptional DDR has been observed in various genome-wide transcript profiling studies that directly monitored ROS-or abiotic stress-mediated responses in Arabidopsis (38, 39).…”

Section: Resultsmentioning

confidence: 99%

Extranuclear protection of chromosomal DNA from oxidative stress

Vanderauwera

Suzuki

Miller

et al. 2011

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

197

138

View full text Add to dashboard Cite

Eukaryotic organisms evolved under aerobic conditions subjecting nuclear DNA to damage provoked by reactive oxygen species (ROS). Although ROS are thought to be a major cause of DNA damage, little is known about the molecular mechanisms protecting nuclear DNA from oxidative stress. Here we show that protection of nuclear DNA in plants requires a coordinated function of ROS-scavenging pathways residing in the cytosol and peroxisomes, demonstrating that nuclear ROS scavengers such as peroxiredoxin and glutathione are insufficient to safeguard DNA integrity. Both catalase (CAT2) and cytosolic ascorbate peroxidase (APX1) play a key role in protecting the plant genome against photorespiratory-dependent H 2 O 2 -induced DNA damage. In apx1/ cat2 double-mutant plants, a DNA damage response is activated, suppressing growth via a WEE1 kinase-dependent cell-cycle checkpoint. This response is correlated with enhanced tolerance to oxidative stress, DNA stress-causing agents, and inhibited programmed cell death.Arabidopsis | stress tolerance | hydrogen peroxide R eactive oxygen species (ROS) are toxic molecules continuously produced in cells during aerobic metabolism. In plants ROS are produced mainly in peroxisomes during photorespiration, in chloroplasts during photosynthesis, and in mitochondria during respiration (1, 2). Unless detoxified by specialized enzymes and low molecular antioxidants, ROS can lead to protein, lipid, and DNA oxidation and to cell death (1, 2). Plants contain a large network of genes encoding different pathways involved in ROS scavenging and production, with a key role in managing the overall steady-state level of ROS in cells (2). Similar to genotoxic agents or ionizing radiation, ROS-derived DNA oxidation leads to altered bases and damaged sugar residues, resulting in DNA single-and double-strand breaks (3, 4). Strand breaks trigger a DNA damage response (DDR) by inducing the expression of molecular markers associated with DNA damage repair, such as poly(ADP ribose) polymerase (PARP), RAD51, and BREAST CANCER (BRCA) family members (5-8). Upon DNA stress, the ataxia telangiectasia-mutated (ATM) and the ataxia telangiectasia and Rad3-related (ATR) signaling kinases are activated and lead, via the WEE1 serine/ threonine kinase, to a transient cell-cycle arrest that allows cells to repair DNA before proceeding into mitosis (9). Although oxidative DNA base damage has been shown to initiate a DDR in mammalian and yeast cells (10, 11), reports in plants on either the sources of oxidative stress that cause DNA damage or the subsequent induction of a DDR directly through ROS remain scarce (3,12,13). Until now, DNA damage and DDR in plants were studied mainly in response to exogenously applied DNAdamaging agents such as bleomycin and hydroxyurea or ionizing irradiation (9, 14, 15).Protection against damage caused by ROS traditionally has been attributed to enzymes with ROS-detoxifying activities (16), and mutants lacking a particular ROS-scavenging enzyme were considered more sensitive to oxidative stress ...

show abstract

Section: Resultsmentioning

confidence: 99%

Extranuclear protection of chromosomal DNA from oxidative stress

Vanderauwera

Suzuki

Miller

et al. 2011

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

197

138

View full text Add to dashboard Cite

show abstract

“…Cells were exposed to different concentrations of resveratrol twice a week for 3 weeks and incubated at 37jC in 95% air/5% CO 2 . Colonies (>100 Am) were scored and photographed after 3 weeks as described previously (24). Western blot analysis.…”

Section: Methodsmentioning

confidence: 99%

“…The supernatant was harvested as cellular protein extract. Protein samples were subjected to immunoblot analysis as described (24). Membranes were probed with antibodies against eEF1A2, actin, phospho-Akt (Ser 473 ), and Akt and blots were visualized according to the procedure described previously (24).…”

Section: Methodsmentioning

confidence: 99%

Resveratrol Suppresses Growth of Human Ovarian Cancer Cells in Culture and in a Murine Xenograft Model: Eukaryotic Elongation Factor 1A2 as a Potential Target

Lee¹,

Choi²,

Kundu³

et al. 2009

Cancer Research

Self Cite

View full text Add to dashboard Cite

The eukaryotic elongation factor 1A2 (eEF1A2) is known to retain oncogenic potential and is recognized as a novel target for cancer prevention and therapy. Resveratrol (trans-3,4 ¶,5-trihydroxystilbene), a phytoalexin present in grapes, has been reported to possess chemopreventive and chemotherapeutic activities. In the present study, we examined the growth-inhibitory effects of resveratrol in human ovarian cancer PA-1 cells, considering eEF1A2 as a potential molecular target. Pretreatment with resveratrol attenuated proliferation of serum-starved PA-1 cells stimulated with insulin or serum. Resveratrol also activated caspase-9, -7, and -3 and induced apoptosis in PA-1 cells in the presence of insulin or serum. Insulin or serum stimulation of PA-1 cells resulted in the marked induction of eEF1A2, which was suppressed by pretreatment with resveratrol. Moreover, resveratrol inhibited insulin-or serum-induced soft-agar colony formation in eEF1A2-transfected NIH3T3 cells. An antibody array directed to assess the phosphorylation of protein kinases revealed that treatment with insulin or serum induced the phosphorylation of Akt in PA-1 cells. Pharmacologic inhibition of Akt with LY294002 abrogated insulin-or serum-induced eEF1A2 expression and increased the caspase-3 activity. In another experiment, i.p. administration of resveratrol retarded the growth of PA-1 cell xenograft and the expression of eEF1A2 in athymic nude mice in association with decreased bromodeoxyuridine positivity, reduced expression of proliferating cell nuclear antigen, increased the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and caspase-3 staining, and diminished CD31 positivity. Taken together, eEF1A2 may be considered as a potential molecular target for the antiproliferative effects of resveratrol in PA-1 ovarian cancer cells.

show abstract

“…MDA-MB-231, MDA-MB-361, MDA-MB-435, HCC1395 and HCC1143 [24,25] were cultured in 5% CO 2 at 37°C in RPMI 1600 (Sigma, St. Louis, MO), supplemented with 10% fetal bovine serum (Atlanta Biologicals, Lawrenceville, GA), 50 units/ml penicillin and 50 μg/ml streptomycin (Invitrogen, Carlsbad, CA). SKBR3 grew in DMEM (Sigma, St. Louis, MO), A1N4 in improved minimal essential medium (IMEM) [26] and MCF-10A in DMEM/F12 (Lonza, Walkersville, MD) [27,28].…”

Section: Cell Lines and Cell Culturementioning

confidence: 99%

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression

Liang

Cho

Williams

et al. 2010

Nucl Med Mol Imaging

View full text Add to dashboard Cite

Purpose L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. Methods LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[ 18 F]fluorocyclobutane-1-carboxylic acid (anti-[ 18 F]FACBC) PET was assessed for its diagnostic biomarker potential. Results Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[ 18 F]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model. Conclusions The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[ 18 F]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.

show abstract

4-Hydroxyestradiol Induces Anchorage-Independent Growth of Human Mammary Epithelial Cells via Activation of IκB Kinase: Potential Role of Reactive Oxygen Species

Cited by 76 publications

References 45 publications

Extranuclear protection of chromosomal DNA from oxidative stress

Extranuclear protection of chromosomal DNA from oxidative stress

Resveratrol Suppresses Growth of Human Ovarian Cancer Cells in Culture and in a Murine Xenograft Model: Eukaryotic Elongation Factor 1A2 as a Potential Target

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression

Contact Info

Product

Resources

About