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Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Mini Review BLCAP (bladder cancer associated protein) Wu Xinxing, Zhao Min, Zuo Zehua School of Medicine, Wuhan University, Wuhan, Hubei, 430071, P.R. China (WX, ZM, ZZ) Published in Atlas Database: May 2008 Online updated version : http://AtlasGeneticsOncology.org/Genes/BLCAPID801ch20q11.html DOI: 10.4267/2042/44444 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology Function Identity BLCAP protein was a member of transmembrane protein 1. By analyzing the signal peptide of BLCAP protein, we found a cleavage site in 63-64 aa. It showed that there might be three phosphorylated sites: 68 aa, 73 aa and 78 aa. In 78-81 aa, a typical [ST]-X(2)-[DE] structure- the phosphorylated site of tyrosine protein kinase was found. Other names: BC10 HGNC (Hugo): BLCAP Location: 20q11.23 Note: Bladder cancer associated protein is a protein which is believed to be involved in the carcinogenesis. Lower levels of BLCAP have been identified in advanced bladder cancer and cervical carcinoma, suggesting a correlation between lower-expression of BLCAP and tumor development. Homology The comparability between the sequences of BLCAP gene and Homo sapiens mRNA (DKFZP564M053) or BC10 was 99% and 87% respectively. DNA/RNA Implicated in Description The BLCAP gene located in chromosome 20q11.2-q12, consists of only one exon and the coding region spans 264 bp. The comparability between the sequences of BLCAP gene and Homo sapiens mRNA (DKFZP564M053) or BC10 was 99% and 87% respectively. Cervical cancer Disease The bladder cancer-associated protein gene (BLCAP) was among the differentially expressed genes in cervical cancer. BLCAP is expressed highly in non cancerous cervical tissues, but it is greatly lost in primary cervical cancer tissue. After transfected BLCAP cDNA into HeLa cells, HeLa cells shows reduced cell growth and clone genicity compared to the vector-transfected cognate cells. BLCAP expression in HeLa cells leads to growth arrest and significantly enhanced apoptosis in vitro and reduced tumor formation in vivo. Protein Description The protein encoded by BLCAP were composite of Leu(19.5%), Pro(9.19%), ser(8.04%), cys(8.04%) and other amino acids. The N-terminal of the protein which was encoded by BLCAP gene was an alpha helix. At the C-terminal, it was beta sheet and in the middle, it was coil. The two terminal regions were more hydrophobile than the middle region. Between 45-65 aa, there was a transmembrane region. Bladder cancer Disease The bladder cancer-associated protein gene (BLCAP, bladder cancer, Mr 10 kDa) was exclusively expressed in the non invasive lesions of bladder cancer. The fulllength bc10 cDNA contains a complete open reading frame (ORF) of 263 bp and encodes a protein composed of 87 amino acids that has no homology to any of the known protein families. Transient expression Expression Expression in human tissues with a relatively low level of expression in cervix, bladder, testis, placenta, spleen and peripheral blood leukocytes. Atlas Genet Cytogenet Oncol Haematol. 2009; 13(4) 258 BLCAP (bladder cancer associated protein) Xinxing W, et al. of bc10 cDNA in COS1 cells yielded a primary translation product with an apparent Mr of 9.8 kDa and pI of 6.7, in agreement with the theoretical calculated value. Comparison of mouse and human bc10 genomic loci revealed an intron less organization of the coding region in both species as well as a highly conserved structure having 91% and 100% identity at the DNA (coding region) and protein levels, respectively. Southern analysis did not reveal gross DNA rearrangements within the bc10 genomic locus in the invasive bladder tumors, implying that the differential expression of the gene most likely reflects alterations in messenger expression (transcription and/or mRNA decay). The downregulation of this novel marker in invasive tumors suggests a putative role in bladder cancer progression. Osteosarcoma Disease The positive rate of BLCAP protein in primary osteosarcoma was very high, much higher than that in recurrent osteosarcoma. It may be helpful for evaluating the prognosis of osteosarcoma to study the relationship between expression of BLCAP protein and malignancy of osteosarcoma. References Gromova I, Gromov P, Celis JE. bc10: A novel human bladder cancer-associated protein with a conserved genomic structure downregulated in invasive cancer. Int J Cancer. 2002 Apr 1;98(4):539-46 Su HC, Zhao YH, Fan DG, Fan QY, Zhang P, Wen YH, Liu YY. [Relationship between expression of BLCAP protein and malignancy of osteosarcoma]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2003 Sep;19(5):465-6 Tongue carcinoma Disease Bladder cancer-associated protein gene (BLCAP) is a novel candidate tumor suppressor gene identified from the human bladder carcinoma. BLCAP overexpression could inhibit cell growth by inducing apoptosis in HeLa cells. Such evidence suggests the alterations in BLCAP may play an important role in tumorigenesis. Overexpressed BLCAP resulted in growth inhibition of the human tongue cancer cell line Tca8113 in vitro, accompanied by S phase cell cycle arrest and apoptosis. The growth inhibition was correlated with upregulation of p21 (WAF1/CIP1) expression and downregulation of Bcl-XL and Bcl-2 expressions. However, p53 expression and NF-kappaB activity remained unchanged post infection. Furthermore, no changes in p53 phosphorylation at Ser46 and nuclear localization, which are critical to p53 function, were observed in BLCAP-overexpressed cells. Taken together, BLCAP may play a role not only in regulating cell proliferation but also in coordinating apoptosis and cell cycle via a novel way independent of p53 and NF-kappaB. Clutterbuck DR, Leroy A, O'Connell MA, Semple CA. A bioinformatic screen for novel A-I RNA editing sites reveals recoding editing in BC10. Bioinformatics. 2005 Jun 1;21(11):2590-5 Evans HK, Weidman JR, Cowley DO, Jirtle RL. Comparative phylogenetic analysis of blcap/nnat reveals eutherian-specific imprinted gene. Mol Biol Evol. 2005 Aug;22(8):1740-8 Zuo Z, Zhao M, Liu J, Gao G, Wu X. Functional analysis of bladder cancer-related protein gene: a putative cervical cancer tumor suppressor gene in cervical carcinoma. Tumour Biol. 2006;27(4):221-6 Zuo ZH, Zhao M, Liu J, Wei Y, Wu XX. [Inhibitory effect of bladder cancer related protein gene on HeLa cell proliferation]. Ai Zheng. 2006 Jul;25(7):811-7 Yao J, Duan L, Fan M, Yuan J, Wu X. Overexpression of BLCAP induces S phase arrest and apoptosis independent of p53 and NF-kappaB in human tongue carcinoma : BLCAP overexpression induces S phase arrest and apoptosis. Mol Cell Biochem. 2007 Mar;297(1-2):81-92 Nishimoto Y, Yamashita T, Hideyama T, Tsuji S, Suzuki N, Kwak S. Determination of editors at the novel A-to-I editing positions. Neurosci Res. 2008 Jun;61(2):201-6 This article should be referenced as such: Xinxing W, Min Z, Zehua Z. BLCAP (bladder cancer associated protein). Atlas Genet Cytogenet Oncol Haematol. 2009; 13(4):258-259. Atlas Genet Cytogenet Oncol Haematol. 2009; 13(4) 259