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Gene Review

NOV  -  nephroblastoma overexpressed

Homo sapiens

Synonyms: CCN family member 3, CCN3, IBP-9, IGF-binding protein 9, IGFBP-9, ...
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Disease relevance of NOV


High impact information on NOV


Chemical compound and disease context of NOV

  • Twenty-two patients affected by relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with a combination of ifosfamide (IFO) at the dose of 1.2 g/m2 intravenous (i.v.) (1 h infusion) for 5 consecutive days with mesna as uroprotector plus mitoxantrone (NOV) at the dose of 12 mg/m2 i.v. on day 1; both drugs were recycled every 3-4 weeks [8].

Biological context of NOV

  • These data suggest that NOV can act as a growth factor for some cells and binds to a specific receptor that leads to the phosphorylation of a 221 kDa protein [9].
  • We have isolated the rat NOV gene, and the DNA sequence shares 90% identity with the mouse and 80% identity with the human sequences [9].
  • These results set the stage for a study of NOVH-fibulin 1C interactions and their potential significance in cell-adhesion signaling in normal and pathological conditions [6].
  • In contrast, CCN3-induced cell migration is dependent on integrins alphavbeta3 and alpha5beta1, whereas alpha6beta1 does not play a role in this process [2].
  • Purified CCN3 supports primary skin fibroblast adhesion through integrins alpha(5)beta(1) and alpha(6)beta(1) and induces fibroblast chemotaxis through integrin alpha(v)beta(5) [7].

Anatomical context of NOV

  • Examination of NOV expression in various human cell lines revealed that NOV was expressed in U87, 293, T98G, SK-N-MC and Hs683 but not in HepG2, HL60, THP1 and Jurkat [9].
  • When 3T3 fibroblasts were treated with this recombinant NOV protein, a dose-dependent increase in proliferation was observed [9].
  • Higher levels of rat NOV mRNA were seen in the brain, lung and skeletal muscle compared to the other tissues [9].
  • Analysis of tyrosine-phosphorylated proteins revealed that when 3T3 cells were treated with NOV, a 221 kDa protein was phosphorylated [9].
  • The rat NOV gene was expressed in all rat tissues examined, including brain, lung, heart, kidney, liver, spleen, thymus and skeletal muscle [9].

Associations of NOV with chemical compounds


Regulatory relationships of NOV

  • There is a possibility that the regulation of NOV expression is different from the pathway regulated by WT1 [12].
  • We also show that the induction of MMP3 in cells expressing NOVH is potentiated by either cell density, serum, or PDGF-BB [13].

Other interactions of NOV


Analytical, diagnostic and therapeutic context of NOV

  • Characterization of human NOV in biological fluids: an enzyme immunoassay for the quantification of human NOV in sera from patients with diseases of the adrenal gland and of the nervous system [4].
  • PTHrP treatment (which inhibits terminal differentiation) decreased NOV expression in murine femurs maintained in organ culture, and decreased the activity of a NOV reporter construct in vitro [19].
  • Reverse transcription polymerse chain reaction (RT-PCR) was used to detect the mRNA expression levels of Cyr61, CTGF and Nov genes in 31 resected specimens of hepatocellular carcinoma and para-cancerous normal liver tissues semi-quantitatively and the relation between their expression levels and clinical pathological parameters were compared [16].
  • Confocal microscopy was used to visualise the nuclear NOV protein in HeLa and 143 cells [20].
  • Western blotting analysis of NOV proteins in both types of fractions was performed using two NOV specific antibodies [20].


  1. Altered expression of novH is associated with human adrenocortical tumorigenesis. Martinerie, C., Gicquel, C., Louvel, A., Laurent, M., Schofield, P.N., Le Bouc, Y. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  2. CCN3 (NOV) is a novel angiogenic regulator of the CCN protein family. Lin, C.G., Leu, S.J., Chen, N., Tebeau, C.M., Lin, S.X., Yeung, C.Y., Lau, L.F. J. Biol. Chem. (2003) [Pubmed]
  3. The expression of ccn3(nov) gene in musculoskeletal tumors. Manara, M.C., Perbal, B., Benini, S., Strammiello, R., Cerisano, V., Perdichizzi, S., Serra, M., Astolfi, A., Bertoni, F., Alami, J., Yeger, H., Picci, P., Scotlandi, K. Am. J. Pathol. (2002) [Pubmed]
  4. Characterization of human NOV in biological fluids: an enzyme immunoassay for the quantification of human NOV in sera from patients with diseases of the adrenal gland and of the nervous system. Thibout, H., Martinerie, C., Créminon, C., Godeau, F., Boudou, P., Le Bouc, Y., Laurent, M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  5. The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family. Brigstock, D.R. Endocr. Rev. (1999) [Pubmed]
  6. The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling. Perbal, B., Martinerie, C., Sainson, R., Werner, M., He, B., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. Integrin-dependent functions of the angiogenic inducer NOV (CCN3): implication in wound healing. Lin, C.G., Chen, C.C., Leu, S.J., Grzeszkiewicz, T.M., Lau, L.F. J. Biol. Chem. (2005) [Pubmed]
  8. Ifosfamide plus mitoxantrone as salvage treatment in non-Hodgkin's lymphomas. Lorusso, V., Paradiso, A., Guida, M., Berardi, F., De Lena, M. Am. J. Clin. Oncol. (1991) [Pubmed]
  9. Nephroblastoma overexpressed gene (NOV) codes for a growth factor that induces protein tyrosine phosphorylation. Liu, C., Liu, X.J., Crowe, P.D., Kelner, G.S., Fan, J., Barry, G., Manu, F., Ling, N., De Souza, E.B., Maki, R.A. Gene (1999) [Pubmed]
  10. The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway. Sakamoto, K., Yamaguchi, S., Ando, R., Miyawaki, A., Kabasawa, Y., Takagi, M., Li, C.L., Perbal, B., Katsube, K. J. Biol. Chem. (2002) [Pubmed]
  11. Adhesion of endothelial cells to NOV is mediated by the integrins alphavbeta3 and alpha5beta1. Ellis, P.D., Metcalfe, J.C., Hyvönen, M., Kemp, P.R. J. Vasc. Res. (2003) [Pubmed]
  12. The expression of NOV and WT1 in renal cell carcinoma: a quantitative reverse transcriptase-polymerase chain reaction analysis. Niu, Z., Ito, M., Awakura, Y., Takahashi, T., Nakamura, E., Ito, N., Ogawa, O. J. Urol. (2005) [Pubmed]
  13. NOVH increases MMP3 expression and cell migration in glioblastoma cells via a PDGFR-alpha-dependent mechanism. Laurent, M., Martinerie, C., Thibout, H., Hoffman, M.P., Verrecchia, F., Le Bouc, Y., Mauviel, A., Kleinman, H.K. FASEB J. (2003) [Pubmed]
  14. Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associated with pre-eclampsia. Gellhaus, A., Schmidt, M., Dunk, C., Lye, S.J., Kimmig, R., Winterhager, E. Mol. Hum. Reprod. (2006) [Pubmed]
  15. NOV/CCN3 impairs muscle cell commitment and differentiation. Calhabeu, F., Lafont, J., Le Dreau, G., Laurent, M., Kazazian, C., Schaeffer, L., Martinerie, C., Dubois, C. Exp. Cell Res. (2006) [Pubmed]
  16. Expressions of cysteine-rich61, connective tissue growth factor and Nov genes in hepatocellular carcinoma and their clinical significance. Zeng, Z.J., Yang, L.Y., Ding, X., Wang, W. World J. Gastroenterol. (2004) [Pubmed]
  17. The expression of novH in adrenocortical cells is down-regulated by TGFbeta 1 through c-Jun in a Smad-independent manner. Lafont, J., Laurent, M., Thibout, H., Lallemand, F., Le Bouc, Y., Atfi, A., Martinerie, C. J. Biol. Chem. (2002) [Pubmed]
  18. Binding properties and distribution of insulin-like growth factor binding protein-related protein 3 (IGFBP-rP3/NovH), an additional member of the IGFBP Superfamily. Burren, C.P., Wilson, E.M., Hwa, V., Oh, Y., Rosenfeld, R.G. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  19. NOV (CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia. Yu, C., Le, A.T., Yeger, H., Perbal, B., Alman, B.A. J. Pathol. (2003) [Pubmed]
  20. Nuclear localisation of NOVH protein: a potential role for NOV in the regulation of gene expression. Perbal, B. MP, Mol. Pathol. (1999) [Pubmed]
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