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MKRNI And HSP90 Expression In Laryngeal Squamous Cell Carcinoma

Posted on:2007-05-24Degree:MasterType:Thesis
Country:ChinaCandidate:S Y WangFull Text:PDF
GTID:2144360182992172Subject:Genetics
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ItruductionTelemorase is positive in the most of immortal cell lines and cacimoma cell which indicated the significant correlation between telomerase activity and carcinoma. Telemorase is composed of hTERT ( human telomerase reverse tran-scriptase) ,hTR( telomerase RNA) and TP1 (telomerase - associated protein 1). In which hTERT plays an important role in regulating telomere length and cell carcinomigenesis. hTERT is,in turn,regulated by a collection of associated factors. Makorin RING finger protein 1 that encoded by gene MKRN1 functions as an E3 ligase and mediates degradation of hTERT . Overexpression of MKRN1 in telomerase positive cells promotes the degradation of hTERT and decreases telomerase activity and subsequently telomere length. The molecular chaperone Hsp90 was another telomerase regulator that play an positive role telomerase activity. Hsp90 binds specifically to hTERT to promote the assembly of active telomerase both in a cell - free system and in intact cells. Disruption of Hsp90 function promotes protesome - mediated degradation of hTERT. The balance between these two genes decides the normal telomerase activity and telomere length, breaking up this balance may lead to disease and cancer. It is still unknown the correlation between MKRN1 and HSP90 , as well as the relationship between these two genes and carcinomigenesis. To investigate if the genes MKRN1 and HSP90 expression was related to laryngeal carcinomigenesis and development, We study the genes expression in Laryngeal Squamous Cell Carcino-ma(LSCC).Materials and methods1. Materials1.1 All 35 LSCC tissues were excised from patients in the first affiliated hospital of China Medical University.1. 2 Reagents for extraction of total RNA.1. 3 Reagents for RT - PCR.2. Methods1) Total RNA was extracted in 35 LSCC and paired adjacent normal tissues as control. The samples that OD260/OD280 > 1. 8 was selected to synthesize cDNA by reverse transcriptation.2 ) PCR was used in gene amplification of MKRNX and HSP90 with p - ac-tin as control.3) Definition of products after electrophoresis.4) SPSS 10. 0 software pack was used in stitistical analysis of the datas.Results1. Down - regulated MKRNX expression was found in 18 tumor tissues (51.4% ) and HSP90 overexpression was found in 16 tumor tissues (45. 7% ) in the 35 LSCC cases. Statistical analysis showed MKRNX expression in tumor tissues was lower than adjacent normal tissues, ( P < 0.01) , HSP90 expression in tumor tissues was higher than adjacent normal tissues(P <0.05) .2. Correlation coefficient between MKRNX and HSP90 expression is r = -0.458(P<0.05).3. HSP90 overexpression was associated with stage of LSCC and age of pa-tients(P <0. 05) . MKRNX expression has no relationship with clinical features of LSCC(P>0.05).ConclusionDown - regulated NKRN and overexpression of HSP90 were found coexisted and correlated to each other in LSCC. Broken of the balance between MKRNX and HSP90 that induced by abnormal expression may play an important role in the carcinomigenesis and development of LSCC.
Keywords/Search Tags:Laryngeal Squamous Cell Carcinoma (LSCC), Makorin RING finger protein 1( MKRN1 ), Heat shock protein 90(HSP90)
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