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Gene Review

BTG2  -  BTG family, member 2

Homo sapiens

Synonyms: BTG family member 2, MGC126063, MGC126064, NGF-inducible anti-proliferative protein PC3, PC3, ...
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Disease relevance of BTG2

  • BTG2 expression was found to be significantly reduced in a large proportion of human kidney and breast carcinomas, suggesting that BTG2 is a tumor suppressor that links p53 and Rb pathways in human tumorigenesis [1].
  • Loss of nuclear BTG2 expression in estrogen receptor-alpha (ERalpha)-positive breast tumors correlated significantly with increased histologic grade and tumor size [2].
  • BTG2 was expressed in all hyperproliferative atrophic peripheral zone lesions examined (simple atrophy, post-atrophic hyperplasia and proliferative inflammatory atrophy), but was undetectable or detectable at very low levels in the hyperproliferative epithelial cells of HGPIN and prostate cancer [3].
  • The BTG2/TIS21/PC3 gene is an antiproliferative gene which maps within a chromosomal segment (1q32) frequently altered in breast adenocarcinomas [4].
  • The neurogene BTG2TIS21/PC3 is transactivated by DeltaNp73alpha via p53 specifically in neuroblastoma cells [5].

High impact information on BTG2


Chemical compound and disease context of BTG2


Biological context of BTG2


Anatomical context of BTG2


Associations of BTG2 with chemical compounds


Physical interactions of BTG2

  • BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms [21].
  • Furthermore, tis21 was bound to cyclin B1 and Cdc2 and inhibited its activity in vivo and in vitro [18].
  • Our results suggest a potential competition between TIS21 and PKC for binding to PICK1 [22].
  • Additionally, we identify a RA response element in the Btg2 promoter and show that the element binds retinoid X receptor/RAR heterodimers in vitro, is occupied by the heterodimers in cells, and can drive RA-induced activation of a reporter gene [23].
  • Overexpressed BTG2 increases PRMT1 participation in the RARalpha protein complex on the RARbeta promoter, a target gene model, and enhances gene-specific histone H4 arginine methylation [20].

Regulatory relationships of BTG2


Other interactions of BTG2

  • As part of an ongoing attempt to understand their biological functions, we used a yeast two-hybrid screening to look for possible functional partners of Btg1 and Btg2 [13].
  • Moreover, we show that hCCR4, as well as hCAF1 and BTG2, modulate the transcription regulation mediated by ERalpha [21].
  • Thus, it can be concluded that the C-terminal regions are necessary and sufficient to control the stabilities of BTG1, BTG2, Tob, and Tob2 proteins [26].
  • Our data indicate that Btg1 and Btg2 act as transcriptional cofactors of the Hoxb9 protein, and suggest that this interaction may mediate their antiproliferative function [13].
  • TIS21 protein modulates the enzymatic activity of recombinant GST-PRMT1 fusion protein but not the activity of GST-PRMT3 [27].

Analytical, diagnostic and therapeutic context of BTG2


  1. A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation. Boiko, A.D., Porteous, S., Razorenova, O.V., Krivokrysenko, V.I., Williams, B.R., Gudkov, A.V. Genes Dev. (2006) [Pubmed]
  2. Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein. Kawakubo, H., Brachtel, E., Hayashida, T., Yeo, G., Kish, J., Muzikansky, A., Walden, P.D., Maheswaran, S. Cancer Res. (2006) [Pubmed]
  3. Antiproliferative B cell translocation gene 2 protein is down-regulated post-transcriptionally as an early event in prostate carcinogenesis. Ficazzola, M.A., Fraiman, M., Gitlin, J., Woo, K., Melamed, J., Rubin, M.A., Walden, P.D. Carcinogenesis (2001) [Pubmed]
  4. The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene. Duriez, C., Falette, N., Audoynaud, C., Moyret-Lalle, C., Bensaad, K., Courtois, S., Wang, Q., Soussi, T., Puisieux, A. Gene (2002) [Pubmed]
  5. The neurogene BTG2TIS21/PC3 is transactivated by DeltaNp73alpha via p53 specifically in neuroblastoma cells. Goldschneider, D., Million, K., Meiller, A., Haddada, H., Puisieux, A., Bénard, J., May, E., Douc-Rasy, S. J. Cell. Sci. (2005) [Pubmed]
  6. Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway. Rouault, J.P., Falette, N., Guéhenneux, F., Guillot, C., Rimokh, R., Wang, Q., Berthet, C., Moyret-Lalle, C., Savatier, P., Pain, B., Shaw, P., Berger, R., Samarut, J., Magaud, J.P., Ozturk, M., Samarut, C., Puisieux, A. Nat. Genet. (1996) [Pubmed]
  7. Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells. Song, X., Lin, H.P., Johnson, A.J., Tseng, P.H., Yang, Y.T., Kulp, S.K., Chen, C.S. J. Natl. Cancer Inst. (2002) [Pubmed]
  8. An androgen-independent androgen receptor function protects from inositol hexakisphosphate toxicity in the PC3/PC3(AR) prostate cancer cell lines. Diallo, J.S., Péant, B., Lessard, L., Delvoye, N., Le Page, C., Mes-Masson, A.M., Saad, F. Prostate (2006) [Pubmed]
  9. Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer. Kuefer, R., Hofer, M.D., Altug, V., Zorn, C., Genze, F., Kunzi-Rapp, K., Hautmann, R.E., Gschwend, J.E. Br. J. Cancer (2004) [Pubmed]
  10. Synergistic antitumor effect of combined use of adenoviral-mediated p53 gene transfer and antisense oligodeoxynucleotide targeting clusterin gene in an androgen-independent human prostate cancer model. Yamanaka, K., Gleave, M.E., Hara, I., Muramaki, M., Miyake, H. Mol. Cancer Ther. (2005) [Pubmed]
  11. Inhibitors of mTOR reverse doxorubicin resistance conferred by PTEN status in prostate cancer cells. Grünwald, V., DeGraffenried, L., Russel, D., Friedrichs, W.E., Ray, R.B., Hidalgo, M. Cancer Res. (2002) [Pubmed]
  12. Prostate-specific antigen (PSA) promoter-driven androgen-inducible expression of sodium iodide symporter in prostate cancer cell lines. Spitzweg, C., Zhang, S., Bergert, E.R., Castro, M.R., McIver, B., Heufelder, A.E., Tindall, D.J., Young, C.Y., Morris, J.C. Cancer Res. (1999) [Pubmed]
  13. The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation. Prévôt, D., Voeltzel, T., Birot, A.M., Morel, A.P., Rostan, M.C., Magaud, J.P., Corbo, L. J. Biol. Chem. (2000) [Pubmed]
  14. Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complex. Rouault, J.P., Prévôt, D., Berthet, C., Birot, A.M., Billaud, M., Magaud, J.P., Corbo, L. J. Biol. Chem. (1998) [Pubmed]
  15. Expression of the NF-kappaB-responsive gene BTG2 is aberrantly regulated in breast cancer. Kawakubo, H., Carey, J.L., Brachtel, E., Gupta, V., Green, J.E., Walden, P.D., Maheswaran, S. Oncogene (2004) [Pubmed]
  16. Identification of genes associated with stromal hyperplasia and glandular atrophy of the prostate by mRNA differential display. Walden, P.D., Lefkowitz, G.K., Ficazzola, M., Gitlin, J., Lepor, H. Exp. Cell Res. (1998) [Pubmed]
  17. BTG2, its family and its tutor. Duriez, C., Moyret-Lalle, C., Falette, N., El-Ghissassi, F., Puisieux, A. Bulletin du cancer. (2004) [Pubmed]
  18. Phosphorylation of serine 147 of tis21/BTG2/pc3 by p-Erk1/2 induces Pin-1 binding in cytoplasm and cell death. Hong, J.W., Ryu, M.S., Lim, I.K. J. Biol. Chem. (2005) [Pubmed]
  19. TIS21/BTG2/PC3 is expressed through PKC-delta pathway and inhibits binding of cyclin B1-Cdc2 and its activity, independent of p53 expression. Ryu, M.S., Lee, M.S., Hong, J.W., Hahn, T.R., Moon, E., Lim, I.K. Exp. Cell Res. (2004) [Pubmed]
  20. Btg2 enhances retinoic acid-induced differentiation by modulating histone H4 methylation and acetylation. Passeri, D., Marcucci, A., Rizzo, G., Billi, M., Panigada, M., Leonardi, L., Tirone, F., Grignani, F. Mol. Cell. Biol. (2006) [Pubmed]
  21. BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms. Morel, A.P., Sentis, S., Bianchin, C., Le Romancer, M., Jonard, L., Rostan, M.C., Rimokh, R., Corbo, L. J. Cell. Sci. (2003) [Pubmed]
  22. Mitogen-stimulated TIS21 protein interacts with a protein-kinase-Calpha-binding protein rPICK1. Lin, W.J., Chang, Y.F., Wang, W.L., Huang, C.Y. Biochem. J. (2001) [Pubmed]
  23. Suppression of mammary carcinoma cell growth by retinoic acid: the cell cycle control gene Btg2 is a direct target for retinoic acid receptor signaling. Donato, L.J., Suh, J.H., Noy, N. Cancer Res. (2007) [Pubmed]
  24. Genistein, a dietary isoflavone, down-regulates the MDM2 oncogene at both transcriptional and posttranslational levels. Li, M., Zhang, Z., Hill, D.L., Chen, X., Wang, H., Zhang, R. Cancer Res. (2005) [Pubmed]
  25. Overexpression of the homeobox gene HOXC8 in human prostate cancer correlates with loss of tumor differentiation. Waltregny, D., Alami, Y., Clausse, N., de Leval, J., Castronovo, V. Prostate (2002) [Pubmed]
  26. Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system. Sasajima, H., Nakagawa, K., Yokosawa, H. Eur. J. Biochem. (2002) [Pubmed]
  27. PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specificity, and regulation. Tang, J., Gary, J.D., Clarke, S., Herschman, H.R. J. Biol. Chem. (1998) [Pubmed]
  28. STAT3 is required but not sufficient for EGF receptor-mediated migration and invasion of human prostate carcinoma cell lines. Zhou, W., Grandis, J.R., Wells, A. Br. J. Cancer (2006) [Pubmed]
  29. TIS21 (/BTG2/PC3) as a link between ageing and cancer: cell cycle regulator and endogenous cell death molecule. Lim, I.K. J. Cancer Res. Clin. Oncol. (2006) [Pubmed]
  30. Impaired expression of the cell cycle regulator BTG2 is common in clear cell renal cell carcinoma. Struckmann, K., Schraml, P., Simon, R., Elmenhorst, K., Mirlacher, M., Kononen, J., Moch, H. Cancer Res. (2004) [Pubmed]
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