LOT1 is a growth suppressor gene down-regulated by the epidermal growth factor receptor ligands and encodes a nuclear zinc-finger protein.

Abstract:

:We previously reported cloning the rLot1 gene, and its human homolog (hLOT1), through analysis of differential gene expression in normal and malignant rat ovarian surface epithelial cells. Both human and rat ovarian carcinoma cell lines exhibited lost or decreased expression of this gene. Interestingly, the LOT1 gene localized at band q25 of human chromosome 6 which is a frequent site for LOH in many solid tumors including ovarian cancer. In this report we have further characterized the potential role of LOT1 in malignant transformation and developed evidence that the gene is a novel target of growth factor signaling pathway. Assays using transient transfections showed that LOT1 is a nuclear protein and may act as a transcription factor. In vitro and in vivo studies involving ovarian cancer cell lines revealed that expression of LOT1 is directly associated with inhibition of cellular proliferation and induction of morphological transformations. Additionally, we show that in normal rat ovarian surface epithelial cells Lot1 gene expression is responsive to growth factor stimulation. Its mRNA is strongly down-regulated by epidermal growth factor receptor (EGFR) ligands, namely EGF and TGF-alpha. Blocking the ligand-activated EGFR signal transduction pathway by the specific EGF receptor inhibitor, tyrphostin AG1478, and the MEK inhibitor, PD098059, restores the normal level of Lot1 gene expression. It appears that the regulation of Lot1 gene is unique to these ligands, as well as the growth promoting agent TPA, since other factors either did not affect Lot1 expression, or the effect was modest and transient. Altogether, the results suggest that Lot1 expression is primarily mediated via EGF receptor or a related pathway and it may regulate the growth promoting signals as a zinc-finger motif containing nuclear transcription factor.

journal_name

Oncogene

journal_title

Oncogene

authors

Abdollahi A,Bao R,Hamilton TC

doi

10.1038/sj.onc.1203067

subject

Has Abstract

pub_date

1999-11-11 00:00:00

pages

6477-87

issue

47

eissn

0950-9232

issn

1476-5594

journal_volume

18

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap.

    abstract::A seven-transmembrane protein, frizzled, has been implicated in a planar cell polarity (PCP) pathway as well as the canonical Wnt signaling pathway. Although both pathways require a cytoplasmic protein, dishevelled, the molecular mechanism by which frizzled regulates intracellular signaling remains to be elucidated. I...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207817

    authors: Yao R,Natsume Y,Noda T

    更新日期:2004-08-12 00:00:00

  • Bcl-2 and calcium: controversy beneath the surface.

    abstract::The function of Bcl-2 family members on the endoplasmic reticulum has received increasing attention in recent years. The endoplasmic reticulum is the major organelle involved in intracellular calcium homeostasis and calcium signaling, including calcium signals that mediate apoptosis induction by anticancer drugs. But ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1207519

    authors: Distelhorst CW,Shore GC

    更新日期:2004-04-12 00:00:00

  • The large E1B protein together with the E4orf6 protein target p53 for active degradation in adenovirus infected cells.

    abstract::It has recently been shown that an adenovirus mutant lacking expression of the large E1B protein (deltaE1B) selectively replicates in p53 deficient cells. However, apart from the large E1B protein the adenovirus early region encodes the E1A and E4orf6 proteins which also have been reported to affect p53 expression as ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201540

    authors: Steegenga WT,Riteco N,Jochemsen AG,Fallaux FJ,Bos JL

    更新日期:1998-01-22 00:00:00

  • p21 suppresses inflammation and tumorigenesis on pRB-deficient stratified epithelia.

    abstract::The retinoblastoma gene product (pRb) controls proliferation and differentiation processes in stratified epithelia. Importantly, and in contrast to other tissues, Rb deficiency does not lead to spontaneous skin tumor formation. As the cyclin-dependent kinase inhibitor p21 regulates proliferation and differentiation in...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.417

    authors: Saiz-Ladera C,Lara MF,Garín M,Ruiz S,Santos M,Lorz C,García-Escudero R,Martínez-Fernández M,Bravo A,Fernández-Capetillo O,Segrelles C,Paramio JM

    更新日期:2014-09-11 00:00:00

  • Regulation of the cell cycle by p53 after DNA damage in an amphibian cell line.

    abstract::In mammalian cells, the p53 protein is a key regulator of the cell cycle following DNA damage. In the present study, we investigated the function of p53 in the A6 amphibian cell line. Using various specific Xenopus p53 monoclonal antibodies, we showed that Xenopus p53 accumulates after DNA damage, including gamma and ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204492

    authors: Bensaad K,Rouillard D,Soussi T

    更新日期:2001-06-28 00:00:00

  • The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers.

    abstract::Transcriptomic screens in breast cancer cell lines have identified a protein named anterior gradient-2 (AGR2) as a potentially novel oncogene overexpressed in estrogen receptor (ER) positive tumours. As targeting the ER is responsible for major improvements in cure rates and prevention of breast cancers, we have evalu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.228

    authors: Hrstka R,Nenutil R,Fourtouna A,Maslon MM,Naughton C,Langdon S,Murray E,Larionov A,Petrakova K,Muller P,Dixon MJ,Hupp TR,Vojtesek B

    更新日期:2010-08-26 00:00:00

  • Growth-dependent and PKC-mediated translational regulation of the upstream stimulating factor-2 (USF2) mRNA in hematopoietic cells.

    abstract::Upstream stimulating factor (USF2) is a basic helix-loop-helix leucine zipper transcription factor, which is found in most tissues. A critical role for USF2 in cellular proliferation has been proposed based on its importance in the regulation of various cyclins and P53 and its capability to antagonize c-myc. In this p...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201584

    authors: Zhang ZC,Nechushtan H,Jacob-Hirsch J,Avni D,Meyuhas O,Razin E

    更新日期:1998-02-12 00:00:00

  • Suppression of Tumorigenicity-14, encoding matriptase, is a critical suppressor of colitis and colitis-associated colon carcinogenesis.

    abstract::Colitis-associated colorectal cancers are an etiologically distinct subgroup of colon cancers that occur in individuals suffering from inflammatory bowel disease and arise as a consequence of persistent exposure of hyperproliferative epithelial stem cells to an inflammatory microenvironment. An intrinsic defect in the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.545

    authors: Kosa P,Szabo R,Molinolo AA,Bugge TH

    更新日期:2012-08-09 00:00:00

  • Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner.

    abstract::Like other types of pre-malignant lesions and carcinoma, angiogenesis is associated with high-grade cervical dysplasia and with invasive squamous carcinoma of the cervix. Vascular endothelial cell growth factor (VEGF) is known to be one of the most important inducers of angiogenesis and is upregulated in carcinoma of ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203817

    authors: López-Ocejo O,Viloria-Petit A,Bequet-Romero M,Mukhopadhyay D,Rak J,Kerbel RS

    更新日期:2000-09-21 00:00:00

  • High incidence of loss of heterozygosity and abnormal imprinting of H19 and IGF2 genes in invasive cervical carcinomas. Uncoupling of H19 and IGF2 expression and biallelic hypomethylation of H19.

    abstract::The few imprinted genes characterized so far include the insulin-like growth factor-2 gene (IGF2) coding for a foetal growth factor and the H19 gene whose normal function is unknown but which is likely to act as an RNA with an antitumour effect. IGF2 is expressed by the paternal allele and H19 by the maternal allele. ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Douc-Rasy S,Barrois M,Fogel S,Ahomadegbe JC,Stéhelin D,Coll J,Riou G

    更新日期:1996-01-18 00:00:00

  • Stable overexpression of MEN1 suppresses tumorigenicity of RAS.

    abstract::Although there is indirect genetic evidence that MEN1, the gene for multiple endocrine neoplasia type 1, is a tumor suppressor gene, little is known about the MEN1-encoded protein, menin. Menin was stably overexpressed in a well-characterized murine tumor cell line, (valine-12)-RAS-transformed NIH3T3 cells. Menin over...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203005

    authors: Kim YS,Burns AL,Goldsmith PK,Heppner C,Park SY,Chandrasekharappa SC,Collins FS,Spiegel AM,Marx SJ

    更新日期:1999-10-21 00:00:00

  • MicroRNA-377 suppresses initiation and progression of esophageal cancer by inhibiting CD133 and VEGF.

    abstract::Esophageal cancer is one of the most lethal cancers worldwide with poor survival and limited therapeutic options. The discovery of microRNAs created a new milestone in cancer research. miR-377 is located in chromosome region 14q32, which is frequently deleted in esophageal squamous cell carcinoma (ESCC), but the biolo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.29

    authors: Li B,Xu WW,Han L,Chan KT,Tsao SW,Lee NPY,Law S,Xu LY,Li EM,Chan KW,Qin YR,Guan XY,He QY,Cheung ALM

    更新日期:2017-07-13 00:00:00

  • Induction of p21Waf1/Cip1 by TNFalpha requires NF-kappaB activity and antagonizes apoptosis in Ewing tumor cells.

    abstract::The Ewing family of tumors is characterized by recurrent reciprocal translocations that generate chimeric proteins, either EWS - FLI-1 or EWS - ERG. These proteins are potent transcriptional activators and are responsible for maintaining the oncogenic properties of tumor cells. Since apoptosis appears to be the main m...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203246

    authors: Javelaud D,Wietzerbin J,Delattre O,Besançon F

    更新日期:2000-01-06 00:00:00

  • Deregulation of p53/p21Cip1/Waf1 pathway contributes to polyploidy and apoptosis of E1A+cHa-ras transformed cells after gamma-irradiation.

    abstract::The p53/p21Cip1/Waf1-dependent checkpoint control of G1/S and G2/M phases of the cell cycle in response to DNA damage is an important mechanism of genome stability maintenance in normal cells. In many tumor cells, due to frequent point mutations and deletions of p53, the stringent control of the cell cycle and apoptos...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202945

    authors: Bulavin DV,Tararova ND,Aksenov ND,Pospelov VA,Pospelova TV

    更新日期:1999-10-07 00:00:00

  • Histone H1(S)-3 phosphorylation in Ha-ras oncogene-transformed mouse fibroblasts.

    abstract::Phosphorylation of linker histone H1(S)-3 (previously named H1b) and core histone H3 is elevated in mouse fibroblasts transformed with oncogenes or constitutively active mitogen-activated protein kinase (MAPK) kinase (MEK). H1(S)-3 phosphorylation is the only histone modification known to be dependent upon transcripti...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206029

    authors: Chadee DN,Peltier CP,Davie JR

    更新日期:2002-12-05 00:00:00

  • A role for mismatch repair in control of DNA ploidy following DNA damage.

    abstract::Many reports have shown a link between mismatch repair (MMR) deficiency and loss of normal cell cycle control, particularly loss of G2 arrest. However almost all of these studies utilized transformed cell lines, and thus the involvement of other genes in this phenotype cannot be excluded. We have examined the effects ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204276

    authors: Strathdee G,Sansom OJ,Sim A,Clarke AR,Brown R

    更新日期:2001-04-05 00:00:00

  • Ligand release-independent transactivation of epidermal growth factor receptor by transforming growth factor-beta involves multiple signaling pathways.

    abstract::Many of the signaling responses induced by transforming growth factor-beta (TGF-beta) are mediated by Smad proteins, but there is evidence that it can also signal independently of Smads. Here, we provide evidence that multiple signal pathways induced by TGF-beta1-including Src family tyrosine kinases (SFKs), generatio...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210649

    authors: Joo CK,Kim HS,Park JY,Seomun Y,Son MJ,Kim JT

    更新日期:2008-01-24 00:00:00

  • v-rel- and c-rel-protein complexes bind to the NF-kappa B site in vitro.

    abstract::Previous work by others has revealed homology between the rel oncogene and the transcription factor NF-kappa B. Further, in vitro-translated v-rel protein and c-rel protein are able to bind to an oligonucleotide containing the kappa B binding site. Unlike the in vitro-translated product, cellular Rel protein exists in...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Kochel T,Rice NR

    更新日期:1992-03-01 00:00:00

  • Loss of p53 induces leukemic transformation in a murine model of Jak2 V617F-driven polycythemia vera.

    abstract::As leukemic transformation of myeloproliferative neoplasms (MPNs) worsens the clinical outcome, reducing the inherent risk of the critical event in MPN cases could be beneficial. Among genetic alterations concerning the transformation, the frequent one is TP53 mutation. Here we show that retroviral overexpression of J...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.478

    authors: Tsuruta-Kishino T,Koya J,Kataoka K,Narukawa K,Sumitomo Y,Kobayashi H,Sato T,Kurokawa M

    更新日期:2017-06-08 00:00:00

  • Endogenous production of leukotriene D4 mediates autocrine survival and proliferation via CysLT1 receptor signalling in intestinal epithelial cells.

    abstract::The cysteinyl leukotriene1 (CysLT1) receptor (CysLT1R) enhances survival and proliferation of intestinal cells via distinct pathways. Here, we have demonstrated that there is significant endogenous production of CysLTs from both non-tumour- and tumour-derived intestinal epithelial cells. Treatment of two non-tumour ce...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209666

    authors: Paruchuri S,Mezhybovska M,Juhas M,Sjölander A

    更新日期:2006-10-26 00:00:00

  • CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation.

    abstract::Dysregulation of cellular signaling pathways can lead to colon cancer. However, research on the key signaling effectors or regulators in colon carcinogenesis is limited. Casein kinase-2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is crucial during adult bone formation and is a promising drug target for osteo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.340

    authors: Nie J,Liu L,Xing G,Zhang M,Wei R,Guo M,Li X,Xie P,Li L,He F,Han W,Zhang L

    更新日期:2014-07-10 00:00:00

  • B-RAF is a therapeutic target in melanoma.

    abstract::B-RAF is a serine/threonine-specific protein kinase that is mutated in approximately 70% of human melanomas. However, the role of this signalling molecule in cancer is unclear. Here, we show that ERK is constitutively activated in melanoma cells expressing oncogenic B-RAF and that this activity is required for prolife...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207785

    authors: Karasarides M,Chiloeches A,Hayward R,Niculescu-Duvaz D,Scanlon I,Friedlos F,Ogilvie L,Hedley D,Martin J,Marshall CJ,Springer CJ,Marais R

    更新日期:2004-08-19 00:00:00

  • Hepatitis B virus X protein promotes the development of liver fibrosis and hepatoma through downregulation of miR-30e targeting P4HA2 mRNA.

    abstract::Hepatitis B virus (HBV)-induced liver necrosis takes great part in liver cirrhosis progression. However, less is known about whether hepatitis B virus X protein (HBx) has effect on liver fibrosis. Here, we report that HBV leads to liver fibrosis and hepatocarcinogenesis through miR-30e targeting P4HA2. HBV transgenic ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.291

    authors: Feng GX,Li J,Yang Z,Zhang SQ,Liu YX,Zhang WY,Ye LH,Zhang XD

    更新日期:2017-12-14 00:00:00

  • Endoplasmic reticulum stress mediates radiation-induced autophagy by perk-eIF2alpha in caspase-3/7-deficient cells.

    abstract::As apoptosis defects limit efficacy of anticancer agents, autophagy has been proposed as a novel strategy for radiotherapy enhancement. We previously showed that caspase-3/7 inhibition induces autophagy and promotes radiosensitivity in vitro and in vivo. Therefore, we further investigated the mechanism by which radiat...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.74

    authors: Kim KW,Moretti L,Mitchell LR,Jung DK,Lu B

    更新日期:2010-06-03 00:00:00

  • Molecular mechanisms of constitutive NF-kappaB/Rel activation in Hodgkin/Reed-Sternberg cells.

    abstract::A common characteristic of malignant cells derived from patients with Hodgkin's disease (HD) is a high level of constitutive nuclear NF-kappaB/Rel activity, which stimulates proliferation and confers resistance to apoptosis. We have analysed the mechanisms that account for NF-kappaB activation in a panel of Hodgkin/Re...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202351

    authors: Krappmann D,Emmerich F,Kordes U,Scharschmidt E,Dörken B,Scheidereit C

    更新日期:1999-01-28 00:00:00

  • Association of extended in vitro proliferative potential with loss of p16INK4 expression.

    abstract::This study addresses the question of whether loss of p16INK4 expression contributes to the immortalization of human cells. In vitro immortalization usually proceeds through two phases. In the first phase (lifespan extension), cells continue proliferating and their telomeres continue shortening beyond the point at whic...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Noble JR,Rogan EM,Neumann AA,Maclean K,Bryan TM,Reddel RR

    更新日期:1996-09-19 00:00:00

  • Differential interaction of plakoglobin and beta-catenin with the ubiquitin-proteasome system.

    abstract::Beta-catenin and plakoglobin are closely related armadillo family proteins with shared and distinct properties; Both are associated with cadherins in actin-containing adherens junctions. Plakoglobin is also found in desmosomes where it anchors intermediate filaments to the desmosomal plaques. Beta-catenin, on the othe...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203519

    authors: Sadot E,Simcha I,Iwai K,Ciechanover A,Geiger B,Ben-Ze'ev A

    更新日期:2000-04-13 00:00:00

  • The three transforming regions of SV40 T antigen are required for immortalization of primary mouse embryo fibroblasts.

    abstract::Simian virus 40 (SV40) is a small DNA tumor virus whose early region gene product, large T antigen, is sufficient to immortalize primary rodent cells and transform established rodent cell lines. Three functional domains of large T antigen are required for transformation of the rat embryo fibroblast REF 52 cell line: t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Conzen SD,Cole CN

    更新日期:1995-12-07 00:00:00

  • Adenovirus E1a as a tumor-suppressor gene.

    abstract::The E1a gene of group C adenoviruses is one of the most studied transforming genes of DNA tumor viruses. These transforming genes have been conventionally considered as dominant oncogenes since they transform cells in vitro and many of the resulting transformed cell lines induce tumors in experimental animals. It now ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:

    authors: Chinnadurai G

    更新日期:1992-07-01 00:00:00

  • The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells.

    abstract::Mutations in p53 change the sensitivity to cancer chemotherapeutic drugs. Whereas many drugs, including the vinca alkaloids, often become less effective when p53 is transcriptionally inactivated, several, most notably paclitaxel, may become more effective. In studying the underlying mechanism(s), we found that increas...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201658

    authors: Zhang CC,Yang JM,White E,Murphy M,Levine A,Hait WN

    更新日期:1998-03-26 00:00:00