Skip to main content
Log in

Effect of regulated expression of the fragile histidine traid gene on cell cycle and proliferation

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The mechanism of tumor suppressor action of the fragile histidine triad (FHIT) gene is unknown. Disruption of cell cycle regulation leads to the tumor formation and many tumor suppressor genes suppress tumorigenesis through their effect on cell cycle regulation. We examined the expression of FHIT during the cell cycle, and determined whether overexpression of FHIT affects cell cycle kinetics and apoptosis. The FHIT cDNA was cloned into the ecdysone-inducible expression vector in both the sense and antisense orientations. Overexpression of the sense or antisense construct did not affect cell proliferation, cell cycle distribution or apoptosis in human 293T cells. Analysis of the FHIT expression in 293T cells collected at various cell cycle phases showed that the expression of FHIT is not under cell cycle regulation. These results indicate that the tumor suppressor activity of the FHIT gene may be independent of an effect on the cell cycle and apoptosis mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Le BM, Drabkin H, Glover TW, Gemmill R, Rassool FV, McKeithan TW, Smith DI: An FHIT tumor suppressor gene? Gene Chrom Cancer 21: 281-289, 1998

    Google Scholar 

  2. Ohta M, Inoue H, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, Et, A: The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinomaassociated t[3, 8] breakpoint, is abnormal in digestive tract cancers. Cell 84: 587-597, 1996

    Google Scholar 

  3. Thiagalingam S, Lisitsyn NA, Hamaguchi M, Wigler MH, Willson JK, Markowitz SD, Leach FS, Kinzler KW, Vogelstein B: Evaluation of the FHIT gene in colorectal cancers. Cancer Res 56: 2936-2939, 1996

    Google Scholar 

  4. Mao L, Fan, YH, Lotan R, Hong WK: Frequent abnormalities of FHIT, a candidate tumor suppressor gene, in head and neck cancer cell lines. Cancer Res 56: 5128-5131, 1996

    Google Scholar 

  5. Panagopoulos I, Pandis N, Thelin S, Petersson C, Mertens F, Borg A, Kristoffersson U, Mitelman F, Aman P: The FHIT and PTPRG genes are deleted in benign proliferative breast disease associated with familial breast cancer and cytogenetic rearrangements of chromosome band 3p14. Cancer Res 56: 4871-4875, 1996

    Google Scholar 

  6. Man S, Ellis IO, Sibbering M, Blamey RW, Brook JD: High levels of allele loss at the FHIT and ATM genes in non-comedo ductal carcinoma in situ and grade I tubular invasive breast cancers. Cancer Res 56: 5484-5489, 1996

    Google Scholar 

  7. Ahmadian M, Wistuba II, Fong KM, Behrens C, Kodagoda DR, Saboorian MH, Shay J, Tomlinson GE, Blum J, Minna JD, Gazdar AF: Analysis of the FHIT gene and FRA3B region in sporadic breast cancer, preneoplastic lesions, and familial breast cancer probands. Cancer Res 57: 3664-3668, 1997

    Google Scholar 

  8. Hayashi S, Tanimoto K, Hajiro Nakanishi K, Tsuchiya E, Kurosumi M, Higashi Y, Imai K, Suga K, Nakachi K: Abnormal FHIT transcripts in human breast carcinomas: A clinicopathological and epidemiological analysis of 61 Japanese cases. Cancer Res 57: 1981-5, 1997

    Google Scholar 

  9. Negrini M, Monaco C, Vorechovsky I, Ohta M, Druck T, Baffa R, Huebner K, Croce CM: The FHIT gene at 3p14.2 is abnormal in breast carcinomas. Cancer Res 56: 3173-3179, 1996

    Google Scholar 

  10. Geurts JM, Schoenmakers EF, Roijer E, Stenman G, Van de Ven WJ: Expression of reciprocal hybrid transcripts of HMGIC and FHIT in a pleomorphic adenoma of the parotid gland. Cancer Res 57: 13-17, 1997

    Google Scholar 

  11. Sozzi G, Alder H, Tornielli S, Corletto V, Baffa R, Veronese ML, Negrini M, Pilotti S, Pierotti MA, Huebner K, Croce CM: Aberrant FHIT transcripts in Merkel cell carcinoma. Cancer Res 56: 2472-2474, 1996

    Google Scholar 

  12. Yanagisawa K, Kondo M, Osada H, Uchida K, Takagi K, Masuda A, Takahashi T: Molecular analysis of the FHIT gene at 3p14.2 in lung cancer cell lines. Cancer Res 56: 5579-5582, 1996

    Google Scholar 

  13. Druck T, Hadaczek P, Fu TB, Ohta M, Siprashvili Z, Baffa R, Negrini M, Kastury K, Veronese ML, Rosen D, Rothstein J, McCue P, Cotticelli MG, Inoue H, Croce CM, Huebner K: Structure and expression of the human FHIT gene in normal and tumor cells. Cancer Res 57: 504-512, 1997

    Google Scholar 

  14. Siprashvili Z, Sozzi G, Barnes LD, McCue P, Robinson AK, Eryomin V, Sard L, Tagliabue E, Greco A, Fusetti L, Schwartz G, Pierotti MA, Croce CM, Huebner K: Replacement of Fhit in cancer cells suppresses tumorigenicity. Proc Natl Acad Sci USA 94: 13771-13776, 1997

    Google Scholar 

  15. Huang Y, Garrison PN, Barnes LD: Cloning of the Schizosaccharomyces pombe gene encoding diadenosine 5′,5‴-P1, P4-tetraphosphate (Ap4 A) asymmetrical hydrolase: Sequence similarity with the histidine triad (HIT) protein family. Biochem J 312: 925-932, 1995

    Google Scholar 

  16. Robinson AK, De la Peña CE, Barnes LD: Isolation and characterization of diadenosine tetraphosphate (Ap4 A) hydrolase from Schizosaccharomyces pombe. Biochim Biophys Acta: Protein Structure and Molecular Enzymology 1161: 139-148, 1993

    Google Scholar 

  17. King KL, Cidlowski JA: Cell cycle regulation and apoptosis. Annu Rev Physiol 60: 601-617, 1998

    Google Scholar 

  18. Numa F, Hirabayashi K, Tsunaga N, Kato H, O'Rourke, K, Shao H, Stechmann LC, Varani J, Rapraeger A, Dixit VM: Elevated levels of syndecan-1 expression confer potent serum-dependent growth in human 293T cells. Cancer Res 55: 4676-4680, 1995

    Google Scholar 

  19. Koda T, Hasan S, Sasaki A, Arimura Y, Kakinuma M: Regulatory sequences required for hst-1 expression in embryonal carcinoma cells. FEBS Lett 342: 71-75, 1994

    Google Scholar 

  20. Pear WS, Nolan GP, Scott ML Baltimore D: Production of hightiter helper-free retroviruses by transient transfection. Proc Natl Acad Sci USA, 90: 8392-8396, 1993

    Google Scholar 

  21. Bell JE, Maines MD: Kinetic properties and regulation of biliverdin reductase. Arch Biochem Biophys 263: 1-9, 1988

    Google Scholar 

  22. Pace HC, Garrison PN, Robinson AK, Barnes LD, Draganescu A, Rosler A, Blackburn GM, Siprashvili Z, Croce CM, Huebner K, Brenner C: Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit. Proc Natl Acad Sci USA 95: 5484-5489, 1998

    Google Scholar 

  23. Kisselev LL, Justesen J, Wolfson AD Frolova LY: Diadenosine oligophosphates (Ap(n)A), a novel class of signaling molecules? FEBS Lett 427: 157-163, 1998

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guo, Z., Vishwanatha, J. Effect of regulated expression of the fragile histidine traid gene on cell cycle and proliferation. Mol Cell Biochem 204, 83–88 (2000). https://doi.org/10.1023/A:1007068823848

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007068823848

Navigation