Expression Of Apoptosis Inhibitor Gene Livin In Bladder Carcinoma And Its Clinical Implication

Bladder cancer is the most neoplasm in Urology in China. Bladdercancer is an important malignancy that occurs worldwide. In>90% of cases,bladder cancer will present as a transitional cell carcinoma. 70% to 80% ofcases are superficial transitional cell carcinoma. Despite the availability ofadequate treatments, the likelihood of recurrence is 50-70% within 5 years,and 15% of superficial tumors may progress to invasive diseases. It is avery important to study the mechanism of the occurrence and developmentof bladder cancer. Programmed cell death, or Apoptosis is an activemechanism of cell death controlling the development and homeostasis ofmulticellular organisms and of inhibiting cancer cells that can product IAPsthat can antiapoptosis. Tight regulation is required to ensure a delicatebalance of life and death. Several types of molecules are known to interferewith apoptosis, for example cellular gene, proteases and signaling pathways.Apoptotic signaling pathways including viral infection, growth factorwithdrawal,Fas/Apo-1(apoptosis activating factor-1),TNF-α/TNFR1 and soon, initiate apoptosis. Death signaling pathways are passed byP53,Caspase,Fas associated death domain FADD,TNF-αreceptor associateddeath domain TRADD and so on. Bcl-2 family, cytochrome c, and Caspaseregulate Apoptosis. These lead to cell death. One of the main apoptoticexecution molecules is Caspase. Two apoptotic pathways have beendescribed. One, Reaper, SMAC/Diablo and HtrA2, is initiated cellapoptosis. Two, Bcl-2, CrmA, P35 and IAPs, is antiapoptosis. The majorregulators of caspases are the IAPs or inhibitors of apoptosis. IAPs wereoriginally identified as a viral protein that blocked apoptosis and inhibit theoccurrence and development of bladder cancer. By a computer database search using the polypeptide consensussequence of the BIR domain of IAP identified an EST clone from a humanfetal kidney cDNAlibrary that encodes a partial BIR consensus sequence,Livin/ML-IAP/KIAP is designated. The Livin gene is located at theterminus of the long arm of chromosome 20,an area that corresponds toband 20q13.This gene was 4.6kb.Using the entire cDNA sequence of Livinas a prode, three distinct mRNAs were detected with approximate sizes of1.4,2.0,and 2.8 kilobases. Livin contains a single BIR domain at the NH2terminus as well a COOH-terminal RING domain. We furtherdemonstrated that Livin encodes two splicing variants, Livinαandβ(20).The two proteins are highly similar, except for 18 amino acids locatedbetween the BIR and the RING domains. The mRNA for Livin was notdetectable by Northern blot in most normal adult tissues with the exceptionof the placenta, but was present in developmental tissues and in severalcancer cell lines. Livin served as a new target for apoptosis-inducingtherapy of cancer. RT-PCR was used to determine the expression of Livin in 36 cases(31 men and 12 women) of TCC and 12 cases of normal bladder tissues(controls). LivinmRNA was expressed in 28 of 36 TCC cases (77.8%). Thepositive rate of Livin expression in T1, T2-4, Ⅰ, Ⅱ, Ⅲ, single, multiple,primary, recurrent was 81.8%(18/22), 71.4%(10/14), 70%(7/10),82.6%(19/23), 66.7%(2/3), 78.9%(15/19), 76.5%(13/17), 80%(20/25),72.7%(8/11). Livin was no correlated with the grade, stage, quantity andrecurrence. There was negative in the control group. The positive rate ofLivin between TCC and control was significant. It is indicated that Livin may play a significant role in the occurrenceof TCC. Livin might be a biomarker for the detection of TCC and served asa new target for apoptosis-inducing therapy of TCC.