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 cervical carcinomas. The fragile histidine triad (FHIT) gene at chromosome region 3p14.2 is a candidate tumor suppressor gene that may play a role in cervical tumorigenesis. We and others have identified aberrant FHIT transcripts and frequent loss of Fhit protein expression in primary cervical cancers and high-grade noninvasive lesions but not in normal cervical tissues. The 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 was to determine whether ectopic expression of Fhit can suppress the tumorigenic properties of cervical cancer cells.


METHODS
We employed infection with recombinant retroviruses as well as transfection of plasmid DNA to restore Fhit protein expression in cervical cancer cell lines lacking full-length FHIT transcripts and endogenous Fhit protein. The effects of Fhit expression on tumor cell morphology, anchorage-independent growth, and tumorigenicity in nude mice were examined.


RESULTS
Stable overexpression of Fhit had no discernible effect on the tumorigenic properties of two cervical carcinoma cell lines or on a lung carcinoma cell line previously reported by others to be suppressed for tumorigenicity by Fhit.


CONCLUSIONS
Restoration of Fhit expression does not suppress anchorage-independent growth or tumorigenicity of cervical carcinoma cell lines. However, it remains possible that FHIT inactivation may be important early in cervical tumor progression or that FHIT may suppress tumorigenesis in ways distinct from those measured by the assays employed in this study.
Wu
R
R
Department of Pathology, The University of Michigan Medical School, Ann Arbor 48109, USA.
Connolly
D C
DC
Dunn
R L
RL
Cho
K R
KR
D017766:Acid Anhydride Hydrolases; D000818:Animals; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012190:Retroviridae; D013274:Stomach Neoplasms / Q000737:chemistry / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000473:pathology*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase