Understanding the mechanisms of FHIT inactivation in cervical cancer for biomarker development

Journal of the Society for Gynecologic Investigation
Jayanthi S LeaCarolyn Y Muller

Abstract

Loss of the fragile histidine triad (Fhit) protein has been documented in cervical cancer and dysplasia. The goal of this study was to confirm the utility of homozygous deletions, aberrant methylation, and immunohistochemical evaluations of FHIT as functionally relevant determinants of FHIT expression. We studied matched DNA, RNA, and protein from nine early-passage cervical cancer cell lines. DNA markers spanning FHIT were used to examine the extent of homozygous deletions for each cell line. 5 CpG island methylation of FHIT was investigated by methylation-specific polymerase chain reaction (PCR) assays. FHIT transcripts were characterized by reverse transcriptase (RT)-PCR. Western blot analysis and immunohistochemistry were performed to characterize Fhit protein expression. Homozygous deletions were found in six of nine cervical cancer cell lines, but only one had homozygous deletions involving an exon. All nine lines had both methylated and unmethylated alleles according to methylation-specific PCR. Loss of wild-type FHIT transcripts were found in five of nine lines. By western blot analysis, Fhit protein expression was lost in five of nine lines, producing an exact correlation with RT-PCR results. Immunohistochemical staini...Continue Reading

References

Feb 3, 1999·Annual Review of Genetics·K HuebnerC M Croce
Dec 10, 1999·International Journal of Cancer. Journal International Du Cancer·K YoshinoY Murata

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Citations

Mar 20, 2012·BMC Veterinary Research·Maria StrazzulloGiuseppe Borzacchiello
Dec 25, 2009·Journal of Cancer Research and Clinical Oncology·Md Imtaiyaz HassanFaizan Ahmad
Jul 9, 2008·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·M Kausar NeyazMausumi Bharadwaj
Jun 21, 2007·The Journal of Obstetrics and Gynaecology Research·Hoenil JoHyo P Lee
Nov 11, 2008·American Journal of Obstetrics and Gynecology·Shawna L Bull PhelpsJayanthi S Lea
Jun 29, 2007·Journal of Lower Genital Tract Disease·Adhemar Longatto-FilhoAdauto Castelo
Sep 5, 2009·Molecular and Cellular Biochemistry·Md Kausar NeyazMausumi Bharadwaj

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