Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma.


:The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro. To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed their expression and biological activity. Comparing Affymetrix DNA-microarray-expression-profiles of CD138-purified plasma-cells from 65 MM-patients and 7 normal individuals to those of plasmablasts and B-cells, we found 5/10 EGF-family genes to be expressed in MMC. Neuregulin-2 and neuregulin-3 were expressed by MMC only, while neuregulin-1, amphiregulin and transforming growth factor-alpha were expressed by both MMC and normal plasma-cells. Using real-time polymerase chain reaction, we found HB-EGF, amphiregulin, neuregulin-1 and epiregulin to be expressed by cells from the bone marrow-environment. Only the EGF-members able to bind heparan-sulphate proteoglycans (HSPGs) - neuregulin-1, amphiregulin, HB-EGF - promote the growth of MMC. Those ligands strongly bind MMC through HSPGs. The binding and the MMC growth activity was abrogated by heparitinase, heparin or deletion of the HS-binding domain. The number of HS-binding EGF ligand molecules bound to MMC was higher than 10(5) molecules/cell and paralleled that of syndecan-1. Syndecan-1, the main HSPG present on MM cells, likely concentrates high levels of HS-binding-EGF-ligands at the cell membrane and facilitates ErbB-activation. Altogether, our data further identify EGF-signalling as promising target for MM-therapy.






Mahtouk K,Cremer FW,Rème T,Jourdan M,Baudard M,Moreaux J,Requirand G,Fiol G,De Vos J,Moos M,Quittet P,Goldschmidt H,Rossi JF,Hose D,Klein B




Has Abstract


2006-11-16 00:00:00
















  • SALL4, a novel marker for human gastric carcinogenesis and metastasis.

    abstract::SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal and pluripotency, has been suggested to be involved in tumorigenesis. The role of SALL4 in human gastric cancer, however, remains largely unknown. In this study, we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein...


    pub_type: 杂志文章


    authors: Zhang L,Xu Z,Xu X,Zhang B,Wu H,Wang M,Zhang X,Yang T,Cai J,Yan Y,Mao F,Zhu W,Shao Q,Qian H,Xu W

    更新日期:2014-11-27 00:00:00

  • Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects.

    abstract::The checkpoint sliding-clamp complex, Rad9/Rad1/Hus1, plays a critical role during initiation of checkpoint signals in response to DNA damage and replication disruption. We investigated the impact of loss of Rad1 on checkpoint function and on DNA replication in mammalian cells. We show that RAD1 is an essential gene f...


    pub_type: 杂志文章


    authors: Bao S,Lu T,Wang X,Zheng H,Wang LE,Wei Q,Hittelman WN,Li L

    更新日期:2004-07-22 00:00:00

  • Activation of MyoD-dependent transcription by cdk9/cyclin T2.

    abstract::Myogenic transcription is repressed in myoblasts by serum-activated cyclin-dependent kinases, such as cdk2 and cdk4. Serum withdrawal promotes muscle-specific gene expression at least in part by down-regulating the activity of these cdks. Unlike the other cdks, cdk9 is not serum- or cell cycle-regulated and is instead...


    pub_type: 杂志文章


    authors: Simone C,Stiegler P,Bagella L,Pucci B,Bellan C,De Falco G,De Luca A,Guanti G,Puri PL,Giordano A

    更新日期:2002-06-13 00:00:00

  • The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF.

    abstract::Tumor necrosis factor (TNF) induces both cell death and survival signals. NF-kappaB, a transcription factor activated by TNF, is critical for controlling survival signals through trans-activation of downstream target genes. However, few NF-kappaB target survival genes have been identified with direct roles in oncogene...


    pub_type: 杂志文章


    authors: Au PY,Martin N,Chau H,Moemeni B,Chia M,Liu FF,Minden M,Yeh WC

    更新日期:2005-04-28 00:00:00

  • Akt regulates nuclear/cytoplasmic localization of tuberin.

    abstract::The autosomal dominantly inherited disease tuberous sclerosis (TSC) affects approximately 1 in 6000 individuals and is characterized by the development of tumors, named hamartomas, in different organs. TSC1, encoding hamartin, and TSC2, encoding tuberin are tumor suppressor genes responsible for TSC. Hamartin and tube...


    pub_type: 杂志文章


    authors: Rosner M,Freilinger A,Hengstschläger M

    更新日期:2007-01-25 00:00:00

  • MAOA-mediated reprogramming of stromal fibroblasts promotes prostate tumorigenesis and cancer stemness.

    abstract::The tumor microenvironment plays a critical role in prostate cancer (PC) development and progression. Inappropriate activation of the stroma potentiates the growth and transformation of epithelial tumor cells. Here, we show that upregulation of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine...


    pub_type: 杂志文章


    authors: Li J,Pu T,Yin L,Li Q,Liao CP,Wu BJ

    更新日期:2020-04-01 00:00:00

  • Synergy of Nf2 and p53 mutations in development of malignant tumours of neural crest origin.

    abstract::Previously, we have mimicked human neurofibromatosis type 2 (NF2) in conditional Nf2 mutant (P0Cre;Nf2flox2/flox2) mice. Schwannomas, characteristic for NF2, were found at low frequency in older mice. Here, we report that these mice, upon additional hemizygosity for p53, rapidly develop multiple tumours showing featur...


    pub_type: 杂志文章


    authors: Robanus-Maandag E,Giovannini M,van der Valk M,Niwa-Kawakita M,Abramowski V,Antonescu C,Thomas G,Berns A

    更新日期:2004-08-26 00:00:00

  • Determination of sequences responsible for the differential regulation of Myc function by delta Max and Max.

    abstract::The DNA-binding, transcriptional activation and transforming activities of the Myc protein require dimerization with Max. Max can form also homodimers which are able to bind the same DNA sequence as Myc/Max heterodimers and suppress Myc-induced transcription and transformation. We have recently identified a naturally ...


    pub_type: 杂志文章


    authors: Västrik I,Mäkelä TP,Koskinen PJ,Alitalo K

    更新日期:1995-08-03 00:00:00

  • Apoptin is modified by SUMO conjugation and targeted to promyelocytic leukemia protein nuclear bodies.

    abstract::Apoptin, a protein of the chicken anemia virus (CAV), represents a novel potential anticancer therapeutic, because it induces apoptotic death specifically in tumor but not normal cells. The cellular localization appears to be crucial for apoptin's selective toxicity. In normal cells apoptin remains in the cytoplasm, w...


    pub_type: 杂志文章


    authors: Janssen K,Hofmann TG,Jans DA,Hay RT,Schulze-Osthoff K,Fischer U

    更新日期:2007-03-08 00:00:00

  • BAG-1 accelerates cell motility of human gastric cancer cells.

    abstract::BAG-1 is a Hsp70/Hsc70-binding protein that interacts with Bcl-2, Raf-1, steroid hormone receptors, Siah-1, and hepatocyte growth factor (HGF) receptors, implying multiple functions for the BAG-1 protein. Here, we provide evidence that gene transfer-mediated overexpression of BAG-1 markedly enhances the motility of hu...


    pub_type: 杂志文章


    authors: Naishiro Y,Adachi M,Okuda H,Yawata A,Mitaka T,Takayama S,Reed JC,Hinoda Y,Imai K

    更新日期:1999-05-27 00:00:00

  • The proto-oncogene RON is involved in development of epithelial, bone and neuro-endocrine tissues.

    abstract::We previously showed that the proto-oncogene RON encodes the tyrosine kinase receptor for Macrophage Stimulating Protein (MSP), originally isolated as a chemotactic factor for peritoneal macrophages. To elucidate the biological role of MSP we studied the expression of the Ron receptor in vivo, and the response to the ...


    pub_type: 杂志文章


    authors: Gaudino G,Avantaggiato V,Follenzi A,Acampora D,Simeone A,Comoglio PM

    更新日期:1995-12-21 00:00:00

  • Alterations in growth properties of human papilloma virus type 16 immortalised human cervical keratinocyte cell line correlate with amplification and overexpression of c-myc oncogene.

    abstract::Clinical and epidemiological data support a role for human papilloma virus (HPV) type 16 in the pathogenesis of cervical carcinoma. The W12 cell line contains HPV16 sequences, predominantly as a high copy number episome, and is immortalised in vitro, but non-tumourigenic. A morphologically distinct sub-line of the par...


    pub_type: 杂志文章


    authors: Crook T,Greenfield I,Howard J,Stanley M

    更新日期:1990-04-01 00:00:00

  • LKB1 inhibits HPV-associated cancer progression by targeting cellular metabolism.

    abstract::Liver kinase B1 (LKB1) is mutationally inactivated in Peutz-Jeghers syndrome and in a variety of cancers including human papillomavirus (HPV)-caused cervical cancer. However, the significance of LKB1 mutations in cervical cancer initiation and progress has not been examined. Herein, we demonstrated that, in mouse embr...


    pub_type: 杂志文章


    authors: Zeng Q,Chen J,Li Y,Werle KD,Zhao RX,Quan CS,Wang YS,Zhai YX,Wang JW,Youssef M,Cui R,Liang J,Genovese N,Chow LT,Li YL,Xu ZX

    更新日期:2017-03-02 00:00:00

  • Copine-I represses NF-kappaB transcription by endoproteolysis of p65.

    abstract::Nuclear factor-kappaB (NF-kappaB) is a dynamic transcription factor that regulates important biological processes involved in cancer initiation and progression. Identifying regulators that control the half-life of NF-kappaB is important to understanding molecular processes that control the duration of transcriptional ...


    pub_type: 杂志文章


    authors: Ramsey CS,Yeung F,Stoddard PB,Li D,Creutz CE,Mayo MW

    更新日期:2008-06-05 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...


    pub_type: 杂志文章


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

    更新日期:1998-03-26 00:00:00

  • Feline STK gene expression in mammary carcinomas.

    abstract::The human RON and its mouse homologue stk are members of the MET family of tyrosine kinase receptors. We have previously shown that the RON gene is over-expressed in human breast carcinomas. As cat mammary tumours have been proposed as a suitable model for aggressive human breast cancer, we identified the feline stk g...


    pub_type: 杂志文章


    authors: De Maria R,Maggiora P,Biolatti B,Prat M,Comoglio PM,Castagnaro M,Di Renzo MF

    更新日期:2002-03-07 00:00:00

  • Influence of Ras and retinoic acid on nerve growth factor induction of transin gene expression in PC12 cells.

    abstract::Nerve growth factor (NGF)- and ras-induced neuronal differentiation of PC12 cells is accompanied by expression of transin, a secreted metalloproteinase. Retinoic acid (RA) is known to exert important effects on neural cell proliferation and differentiation. In this study we have analysed different PC12 sublines which ...


    pub_type: 杂志文章


    authors: Cosgaya JM,Recio JA,Aranda A

    更新日期:1997-04-10 00:00:00

  • Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation.

    abstract::The Cbl family proteins Cbl, Cbl-b, and Cbl-c/Cbl-3 are thought to regulate signaling through protein-tyrosine kinases, positively as scaffold proteins and negatively as ubiquitin ligases. However, the precise signaling pathways and target proteins for each Cbl family member are not well understood. Here we show that ...


    pub_type: 杂志文章


    authors: Kim M,Tezuka T,Tanaka K,Yamamoto T

    更新日期:2004-03-04 00:00:00

  • HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma.

    abstract::Hepatocyte nuclear factor 4alpha (HNF4alpha) is a tissue-specific transcription factor known to regulate a large number of genes in hepatocytes and pancreatic beta cells. Although HNF4alpha is highly expressed in some sections of the kidney, little is known about its role in this organ and about HNF4alpha-regulated ge...


    pub_type: 杂志文章


    authors: Lucas B,Grigo K,Erdmann S,Lausen J,Klein-Hitpass L,Ryffel GU

    更新日期:2005-09-22 00:00:00

  • Stanniocalcin-1 acts in a negative feedback loop in the prosurvival ERK1/2 signaling pathway during oxidative stress.

    abstract::Mammalian Stanniocalcin-1 (STC1) is a glycoprotein that has been implicated in various biological processes including angiogenesis. Aberrant STC1 expression has been reported in breast, ovarian and prostate cancers, but the significance of this is not well understood. Here, we report that oxidative stress caused a 40-...


    pub_type: 杂志文章


    authors: Nguyen A,Chang AC,Reddel RR

    更新日期:2009-05-07 00:00:00

  • Interferon-induces expression of cyclin-dependent kinase-inhibitors p21WAF1 and p27Kip1 that prevent activation of cyclin-dependent kinase by CDK-activating kinase (CAK).

    abstract::To understand the mechanism of interferon (IFN)-mediated suppression of cell cycle progression, we have earlier shown that IFN-alpha enhances the expression of underphosphorylated retinoblastoma protein by inhibiting the cyclin-dependent kinase-2 (CDK-2) activity (Kumar and Atlas, Proc. Natl. Acad. Sci. 89, 6599-6603,...


    pub_type: 杂志文章


    authors: Mandal M,Bandyopadhyay D,Goepfert TM,Kumar R

    更新日期:1998-01-15 00:00:00

  • ATF-2 controls transcription of Maspin and GADD45 alpha genes independently from p53 to suppress mammary tumors.

    abstract::The activating transcription factor, ATF-2, is a target of p38 and JNK that are involved in stress-induced apoptosis. Heterozygous Atf-2 mutant (Atf-2+/-) mice are highly prone to mammary tumors. The apoptosis-regulated gene GADD45alpha and the breast cancer suppressor gene Maspin, both of which are known to be p53 ta...


    pub_type: 杂志文章


    authors: Maekawa T,Sano Y,Shinagawa T,Rahman Z,Sakuma T,Nomura S,Licht JD,Ishii S

    更新日期:2008-02-14 00:00:00

  • Repression of hepatitis B virus (HBV) transgene and HBV-induced liver injury by low protein diet.

    abstract::Persistent infection with hepatitis B virus (HBV) is one of the primary risk factors for human hepatocellular carcinoma (HCC). In a human ecological study, we have shown that, in addition to HBV, animal food consumption also significantly contributes to the variance of HCC. To test the interacting effect of HBV and an...


    pub_type: 杂志文章


    authors: Hu JF,Cheng Z,Chisari FV,Vu TH,Hoffman AR,Campbell TC

    更新日期:1997-12-04 00:00:00

  • Electron microscopy and 3D reconstructions reveal that human ATM kinase uses an arm-like domain to clamp around double-stranded DNA.

    abstract::The human tumor suppressor gene ataxia telangiectasia mutated (ATM) encodes a 3056 amino-acid protein kinase that regulates cell cycle checkpoints. ATM is defective in the neurodegenerative and cancer predisposition syndrome ataxia-telangiectasia. ATM protein kinase is activated by DNA damage and responds by phosphory...


    pub_type: 杂志文章


    authors: Llorca O,Rivera-Calzada A,Grantham J,Willison KR

    更新日期:2003-06-19 00:00:00

  • Caspase-dependent processing activates the proapoptotic activity of deleted in breast cancer-1 during tumor necrosis factor-alpha-mediated death signaling.

    abstract::Deleted in breast cancer-1 (DBC-1) was initially cloned from a homozygously deleted region in breast and other cancers on human chromosome 8p21, although no function is known for the protein product it encodes. We identified the generation of amino-terminally truncated versions of DBC-1 during tumor necrosis factor (T...


    pub_type: 杂志文章


    authors: Sundararajan R,Chen G,Mukherjee C,White E

    更新日期:2005-07-21 00:00:00

  • Ligand-associated ERBB2/3 activation confers acquired resistance to FGFR inhibition in FGFR3-dependent cancer cells.

    abstract::Somatic alterations of fibroblast growth factor receptors (FGFRs) have been described in a wide range of malignancies. A number of anti-FGFR therapies are currently under investigation in clinical trials for subjects with FGFR gene amplifications, mutations and translocations. Here, we develop cell line models of acqu...


    pub_type: 杂志文章


    authors: Wang J,Mikse O,Liao RG,Li Y,Tan L,Janne PA,Gray NS,Wong KK,Hammerman PS

    更新日期:2015-04-23 00:00:00

  • Anthracyclines induce the accumulation of mutant p53 through E2F1-dependent and -independent mechanisms.

    abstract::Mutant p53 frequently accumulates in cancer cells and promotes tumor cell invasion, as part of its gain of function. Its accumulation is partially due to enhanced stability, but little is known about how the mRNA levels of mutant p53 can be regulated. Likewise, the impact of cancer therapy on the levels of mutant p53 ...


    pub_type: 杂志文章


    authors: Bug M,Dobbelstein M

    更新日期:2011-08-18 00:00:00

  • The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family.

    abstract::Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the end...


    pub_type: 杂志文章,评审


    authors: Heath-Engel HM,Chang NC,Shore GC

    更新日期:2008-10-27 00:00:00

  • C5a induces A549 cell proliferation of non-small cell lung cancer via GDF15 gene activation mediated by GCN5-dependent KLF5 acetylation.

    abstract::Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the pr...


    pub_type: 杂志文章


    authors: Zhao C,Li Y,Qiu W,He F,Zhang W,Zhao D,Zhang Z,Zhang E,Ma P,Liu Y,Ma L,Yang F,Wang Y,Shu Y

    更新日期:2018-08-01 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...


    pub_type: 杂志文章


    authors: Kochel T,Rice NR

    更新日期:1992-03-01 00:00:00