20q11.23

Cervical cancer

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.

Bladder cancer

The bladder cancer-associated protein gene (BLCAP, bladder cancer, Mr 10 kDa) was exclusively expressed in the non invasive lesions of bladder cancer. The full-length 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 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.

Tongue carcinoma

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 up-regulation of p21 (WAF1/CIP1 ) expression and down-regulation 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.

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.