Restored expression of fragile histidine triad protein and tumorigenicity of cervical carcinoma cells

Background: Allelic losses in the short arm of chromosome 3 are common in c ervical carcinomas. The fragile histidine triad (FHIT) gene at chromosome r egion 3p14.2 is a candidate tumor suppressor gene that may play a role in c ervical tumorigenesis. We and others have identified aberrant FHIT transcri pts and frequent loss of Fhit protein expression in primary cervical cancer s and high-grade noninvasive lesions but not in normal cervical tissues. Th e altered expression of FHIT may be due to somatic mutations or integration of human papillomavirus DNA at the FHIT locus. The purpose of this study w as to determine whether ectopic expression of Fhit can suppress the tumorig enic properties of cervical cancer cells. Methods: We employed infection wi th recombinant retroviruses as well as transfection of plasmid DNA to resto re Fhit protein expression in cervical cancer cell Lines lacking full-lengt h FHIT transcripts and endogenous Fhit protein. The effects of Fhit express ion on tumor cell morphology, anchorage-independent growth, and tumorigenic ity in nude mice were examined. Results: Stable overexpression of Fhit had no discernible effect on the tumorigenic properties of two cervical carcino ma cell lines or on a lung carcinoma cell line previously reported by other s to be suppressed for tumorigenicity by Fhit. Conclusions: Restoration of Fhit expression does not suppress anchorage-independent growth or tumorigen icity of cervical carcinoma cell lines. However, it remains possible that F HIT inactivation may be important early in cervical tumor progression or th at FHIT may suppress tumorigenesis in ways distinct from those measured by the assays employed in this study.