TIS21/BTG2 Negatively Regulates Estradiol-Stimulated Expansion of Hematopoietic Stem Cells by Derepressing Akt Phosphorylation and Inhibiting mTOR Signal Transduction

Kim, Bong Cho; Ryu, Min Sook; Oh, Seh–Hoon; Lim, In Kyoung

doi:10.1634/stemcells.2008-0327

Cited by 25 publications

(18 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ϫ/Ϫ MEF (24,30,31). As opposed to TIS21 ϩ/ϩ MEF, exposure of TIS21 Ϫ/Ϫ MEF to DOXO demonstrated a lower number of viable cells, suggesting the anti-apoptotic role of TIS21 gene in MEF (Fig.…”

Section: No Protective Effect Of Nac On Doxo-induced Mef Cell Death-mentioning

confidence: 92%

B Cell Translocation Gene 2 Enhances Susceptibility of HeLa Cells to Doxorubicin-induced Oxidative Damage

Lim

Park

Lim

2008

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

BTG2/TIS21/PC3 (B cell translocation gene 2) has been known as a p53 target gene and functions as a tumor suppressor in carcinogenesis of thymus, prostate, kidney, and liver. Although it has been known that the expression of BTG2 /TIS21/PC3 is induced during chemotherapy-mediated apoptosis in cancer cells, a role of BTG2 /TIS21/PC3 in cell death remains to be elucidated. In this study, the mechanism and role of BTG2 involved in the enhancement of doxorubicin ( TIS21(12-O-tetradecanoylphorbol-13-acetate-inducible sequence 21) was first identified as one of immediate early genes (1) in mice 3T3 fibroblasts when treated with 12-O-tetradecanoylphorbol-13-acetate (2). Since then, PC3 (pheochromocytoma cell 3) was isolated as an immediate early response gene when activated by nerve growth factor at the onset of neuronal differentiation in rat PC12 cells (3). The human homolog of TIS21, named BTG2 (B cell translocation gene 2), was cloned from a cDNA library of human lymphoblastoid cells as a gene associated with DNA damage response and contains p53 response elements in its 5Ј-flanking (Ϫ74 to Ϫ112) region (4).We previously reported that TIS21 expression was low in thymic carcinoma developed in the SV40 large T antigen transgenic mice but high in normal thymus, suggesting anticarcinogenic activity of TIS21 in thymus (5). Expressions of TIS21 in renal proximal tubule and prostate acini are lost also in the renal carcinoma and the early stage of carcinogenesis in prostate (6, 7), respectively. Consistent with these findings, Boiko et al. (8) recently ascertained BTG2 as a tumor suppressor by showing that BTG2 is a major downstream effector of p53-dependent proliferation arrest of mouse and human fibroblasts transduced with oncogenic Ras and that repression of BTG2 regulates the activities of cyclin D1 and cyclin E and phosphorylation of pRB, thus inducing neoplastic transformation of primary human fibroblasts. TIS21 has been known to work also independently of pRB and p53 in cancer cells regulating G 1 /S arrest and G 2 /M arrest by inhibiting synthesis of cyclin E and cdk4 (9), as well as interaction with cyclin B1 and the cdk1 complex (10), respectively. Moreover, persistent expression of TIS21 induces the loss of mitochondrial membrane potential differences in U937 cells (11), and transfection of TIS21 gene to Huh7 hepatoma cells significantly reduces in vivo and in vitro tumorigenesis by inhibiting feedback regulation between cyclin B1 and FoxM1 transcription factor (11), and the expression of BTG2 in human liver cancer is much lower than that of the surrounding tissues. Collectively, these findings indicate that TIS21 controls cellular process as an inhibitor of cell division cycle and a tumor suppressor, thus evading cancer development independent of p53.The level of reactive oxygen species (ROS) 2 is controlled by multiple interacting components. Among them, superoxide dismutase (SOD), glutathione peroxidase 1 (GPx), and catalase are the primary antioxidant enzymes in mammalian tissues (12,13). SOD catalyzes di...

show abstract

Section: No Protective Effect Of Nac On Doxo-induced Mef Cell Death-mentioning

confidence: 92%

B Cell Translocation Gene 2 Enhances Susceptibility of HeLa Cells to Doxorubicin-induced Oxidative Damage

Lim

Park

Lim

2008

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Preparation of Ad-Btg2 has been described in our previous reports [14,19]. For HL-60 cells, Ad-Btg2, infection was performed with 10 μg/ml polybrene (1,5-dimethyl-1,5-diazaundecamethylene polymethobromide).…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

“…Mouse TIS21 [11] and rat PC3 [12] are homologs of human B-cell translocation gene-2 (BTG2). The data accumulated during the past two decades with both cells and animal models implicate Btg2/TIS21/PC3 (Btg2) in a variety of biological processes such as mediation of stage specific expansion of developing thymocytes [13], regulation of the hematopoietic progenitor cell expansion in response to estradiol [14], cell cycle arrest at G2/M [15] and G1/S phases [16,17], enhancement of cancer cell death via interaction with Pin-1 in response to growth factor stimulation [18] or via accumulation of hydrogen peroxide after doxorubicin treatment [19], and regulation of neuronal differentiation [20,21]. Moreover, Btg2 is involved in the differentiation of myelocytic leukemia cells and CD34 + hematopoietic precursor cells [22,23], DNA repair [24,25], inhibition of cancer cell migration [26], as a transcriptional co-regulator in different model systems, and in the antioxidant defenses through the antioxidant transcription factor NFE2L2 [22,27].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Btg2/TIS21/PC3 expression via reactive oxygen species–protein kinase C–ΝFκΒ pathway under stress conditions

Imran

Lim

2013

Cellular Signalling

Self Cite

View full text Add to dashboard Cite

“…Furthermore, activations of Akt and mammalian target of rapamycin in bone marrow stem cells and TIS21 − / − mouse embryonic fibroblasts (MEF) are reciprocally regulated after estradiol treatment. 32 In the present study, we attempted to characterize in more detail how TIS21 /BTG2/Pc3 regulates the invasive behavior and what is its signaling pathway in the highly invasive breast cancer cells by using transduction of adenovirus-carrying TIS21 gene (Ad-TIS21) and investigating actin polymerization by actin nucleators, mDia genes, through 'Akt1-Sp1-Nox4-ROS' pathway.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of breast cancer invasion by TIS21/BTG2/Pc3-Akt1-Sp1-Nox4 pathway targeting actin nucleators, mDia genes

Jung

et al. 2015

Oncogene

View full text Add to dashboard Cite

The mammalian homolog of Drosophila diaphanous (mDia), actin nucleator, has been known to participate in the process of invasion and metastasis of cancer cells via regulating a number of actin-related biological processes. We have previously reported that tumor suppressor TIS21(/BTG2/Pc3) (TIS21) inhibits invadopodia formation by downregulating reactive oxygen species (ROS) in MDA-MB-231 cells. We herein report that TIS21(/BTG2/Pc3) downregulates diaphanous-related formin (DRF) expression via reducing NADPH oxidase 4 (Nox4)-derived ROS generation by Akt1 activation and subsequently impairs invasion activity of the highly invasive breast cancer cells. Knockdown of Akt1 by RNA interference recovered the TIS21(/BTG2/Pc3)-inhibited F-actin remodeling and ROS generation by recovering Nox4 expression. Furthermore, Sp1-mediated Nox4 transcription was downregulated by TIS21(/BTG2/Pc3)-Akt1 signals, leading to the inhibition of cancer cell invasion via F-actin remodeling by mDia genes. To our best knowledge, this is the first study to show that TIS21(/BTG2/Pc3)-Akt1 inhibited Sp1-Nox4-ROS cascade, subsequently reducing invasion activity via inhibition of mDia family genes.

show abstract

TIS21/BTG2 Negatively Regulates Estradiol-Stimulated Expansion of Hematopoietic Stem Cells by Derepressing Akt Phosphorylation and Inhibiting mTOR Signal Transduction

Abstract: ABSTRACT

Cited by 25 publications

References 54 publications

B Cell Translocation Gene 2 Enhances Susceptibility of HeLa Cells to Doxorubicin-induced Oxidative Damage

B Cell Translocation Gene 2 Enhances Susceptibility of HeLa Cells to Doxorubicin-induced Oxidative Damage

Regulation of Btg2/TIS21/PC3 expression via reactive oxygen species–protein kinase C–ΝFκΒ pathway under stress conditions

Inhibition of breast cancer invasion by TIS21/BTG2/Pc3-Akt1-Sp1-Nox4 pathway targeting actin nucleators, mDia genes

Contact Info

Product

Resources

About