| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 [D. L. G., D. C. C., R. W., R. Y. L., J. T. C. V., K. R. C.]; Department of Obstetrics and Gynecology, Asan Medical Center and School of Medicine, University of Ulsan, Seoul, 138-040, Korea [Y-T. K., J. E. M.]; International Agency for Research on Cancer, 69372 Lyon, Cedex 08, France [N. M.]; Servei D'Epidemiologia I Registre Del Càncer, Institut Català D'Oncologia, E-08907 L'Hospitalet Del Llobregat, Barcelona, Spain [F. X B.]; and Department of Microbiology and Immunology, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205 [K. S.]
Allelic deletions involving the short arm of chromosome 3 (3p13–21.1) have been observed frequently in cervical carcinomas. Recently, a candidate tumor suppressor gene, FHIT (Fragile Histidine Triad), was cloned and mapped to this chromosomal region (3p14.2). Abnormal FHIT transcripts have been identified previously in a variety of tumor cell lines and primary carcinomas, although their significance and the molecular mechanisms underlying their origin remain incompletely defined. In addition, integration of human papillomavirus DNA has been identified at a fragile site (FRA3B) within the FHIT locus in cervical cancer. These observations motivated us to evaluate FHIT mRNA and protein expression in cervical cancer cell lines, primary cervical carcinomas, and normal tissues. Transcripts of the expected size and sequence were the predominant species identified by reverse transcription (RT)-PCR in cultured keratinocytes and all normal tissues evaluated. In contrast, aberrant FHIT transcripts were readily demonstrated in 6 of 7 cervical carcinoma cell lines and 17 of 25 (68%) primary cervical carcinomas. Northern blot analyses demonstrated reduced or absent FHIT expression in the cervical carcinoma cell lines, particularly those with aberrant RT-PCR products. Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76%) primary cervical carcinomas. In those cervical cancer cell lines and primary tumors with exclusively aberrant or absent FHIT transcripts by RT-PCR, Fhit protein expression was always markedly reduced or absent. The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.
1 This work was supported by the Richard W. TeLinde endowment, funds from the Caring Collection, and Grant CA 64466 from the NIH (to K. R. C.).
2 These individuals contributed equally to the work reported in this study.
3 To whom requests for reprints should be addressed, at Department of Pathology, The Johns Hopkins University School of Medicine, Room 659, Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205.
Received 8/11/97. Accepted 9/22/97.
This article has been cited by other articles:
|
|
 |
|
  S. Brandt, R. Haralambus, A. Schoster, R. Kirnbauer, and C. Stanek Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines J. Gen. Virol., June 1, 2008; 89(6): 1390 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bavi, Z. Jehan, V. Atizado, H. Al-Dossari, F. Al-Dayel, A. Tulbah, S. S. Amr, S. S. Sheikh, A. Ezzat, H. El-Solh, et al. Prevalence of fragile histidine triad expression in tumors from saudi arabia: a tissue microarray analysis. Cancer Epidemiol. Biomarkers Prev., September 1, 2006; 15(9): 1708 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Holschneider, R. L. Baldwin, K. Tumber, C. Aoyama, and B. Y. Karlan The Fragile Histidine Triad Gene: A Molecular Link Between Cigarette Smoking and Cervical Cancer Clin. Cancer Res., August 15, 2005; 11(16): 5756 - 5763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Arun, G. Kilic, C. Yen, B. Foster, D. A. Yardley, R. Gaynor, and R. Ashfaq Loss of FHIT Expression in Breast Cancer Is Correlated with Poor Prognostic Markers Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1681 - 1685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-K. Tai, J. I. Lee, K. K. Ang, A. K. El-Naggar, K. A. Hassan, D. Liu, J. J. Lee, H. Ren, W. K. Hong, and L. Mao Loss of Fhit Expression in Head and Neck Squamous Cell Carcinoma and Its Potential Clinical Implication Clin. Cancer Res., August 15, 2004; 10(16): 5554 - 5557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Lea, R. Ashfaq, S. Muneer, D. G. Burbee, D. S. Miller, J. D. Minna, and C. Y. Muller Understanding the Mechanisms of FHIT Inactivation in Cervical Cancer for Biomarker Development Reproductive Sciences, July 1, 2004; 11(5): 329 - 337. [Abstract] [PDF]
|
|
|
|
 |
|
 S. M. Kraggerud, P. Aman, R. Holm, A. E. Stenwig, S. D. Fossa, J. M. Nesland, and R. A. Lothe Alterations of the Fragile Histidine Triad Gene, FHIT, and Its Encoded Products Contribute to Testicular Germ Cell Tumorigenesis Cancer Res., January 1, 2002; 62(2): 512 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Krivak, J. W. McBroom, J. Seidman, D. Venzon, B. Crothers, P. J. MacKoul, G. S. Rose, J. W. Carlson, and M. J. Birrer Abnormal Fragile Histidine Triad (FHIT) Expression in Advanced Cervical Carcinoma: A Poor Prognostic Factor Cancer Res., June 1, 2001; 61(11): 4382 - 4385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vecchione, N. Zanesi, G. Trombetta, D. French, P. Visca, T. Pisani, C. Botti, A. Vecchione, C. M. Croce, and R. Mancini Cervical Dysplasia, Ploidy, and Human Papillomavirus Status Correlate with Loss of Fhit Expression Clin. Cancer Res., May 1, 2001; 7(5): 1306 - 1312. [Abstract] [Full Text]
|
|
|
|
|
|
J. I. Lee, J.-C. Soria, K. Hassan, D. Liu, X. Tang, A. El-Naggar, W. K. Hong, and L. Mao Loss of Fhit Expression Is a Predictor of Poor Outcome in Tongue Cancer Cancer Res., February 1, 2001; 61(3): 837 - 841. [Abstract] [Full Text]
|
|
|
|
|
|
I. D. Kholodnyuk, A. Szeles, Y. Yang, G. Klein, and S. Imreh Inactivation of the Human Fragile Histidine Triad Gene at 3p14.2 in Monochromosomal Human/Mouse Microcell Hybrid-derived Severe Combined Immunodeficient Mouse Tumors Cancer Res., December 1, 2000; 60(24): 7119 - 7125. [Abstract] [Full Text]
|
|
|
|
|
|
D. C. Connolly, D. L. Greenspan, R. Wu, X. Ren, R. L. Dunn, K. V. Shah, R. W. Jones, F. X. Bosch, N. Muñoz, and K. R. Cho Loss of Fhit Expression in Invasive Cervical Carcinomas and Intraepithelial Lesions Associated with Invasive Disease Clin. Cancer Res., September 1, 2000; 6(9): 3505 - 3510. [Abstract] [Full Text]
|
|
|
|
|
|
Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax Expression in Invasive and in Situ Squamous Cell Carcinoma of the Uterine Cervix Clin. Cancer Res., September 1, 2000; 6(9): 3600 - 3606. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Wu, D. C. Connolly, R. L. Dunn, and K. R. Cho Restored Expression of Fragile Histidine Triad Protein and Tumorigenicity of Cervical Carcinoma Cells J Natl Cancer Inst, February 16, 2000; 92(4): 338 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Baffa, L. G. Gomella, A. Vecchione, P. Bassi, K. Mimori, J. Sedor, C. M. Calviello, M. Gardiman, C. Minimo, S. E. Strup, et al. Loss of FHIT Expression in Transitional Cell Carcinoma of the Urinary Bladder Am. J. Pathol., February 1, 2000; 156(2): 419 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Kantarjian, M. Talpaz, S. O'Brien, T. Manshouri, J. Cortes, F. Giles, M. B. Rios, C. M. Croce, and M. Albitar Significance of FHIT Expression in Chronic Myelogenous Leukemia Clin. Cancer Res., December 1, 1999; 5(12): 4059 - 4064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Koopman, K. Szuhai, J. D. H. van Eendenburg, V. Bezrookove, G. G. Kenter, E. Schuuring, H. Tanke, and G. Jan Fleuren Recurrent Integration of Human Papillomaviruses 16, 45, and 67 Near Translocation Breakpoints in New Cervical Cancer Cell Lines Cancer Res., November 1, 1999; 59(21): 5615 - 5624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Tseng, B. L. Kemp, F. R. Khuri, J. M. Kurie, J. S. Lee, X. Zhou, D. Liu, W. K. Hong, and L. Mao Loss of Fhit Is Frequent in Stage I Non-Small Cell Lung Cancer and in the Lungs of Chronic Smokers Cancer Res., October 1, 1999; 59(19): 4798 - 4803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Birrer, D. Hendricks, J. Farley, M. J. Sundborg, T. Bonome, M. J. Walts, and J. Geradts Abnormal Fhit Expression in Malignant and Premalignant Lesions of the Cervix Cancer Res., October 1, 1999; 59(20): 5270 - 5274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hallas, M. Albitar, J. Letofsky, M. J. Keating, K. Huebner, and C. M. Croce Loss of FHIT Expression in Acute Lymphoblastic Leukemia Clin. Cancer Res., September 1, 1999; 5(9): 2409 - 2414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sard, P. Accornero, S. Tornielli, D. Delia, G. Bunone, M. Campiglio, M. P. Colombo, M. Gramegna, C. M. Croce, M. A. Pierotti, et al. The tumor-suppressor gene FHIT is involved in the regulation of apoptosis and in cell cycle control PNAS, July 20, 1999; 96(15): 8489 - 8492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ji, B. Fang, N. Yen, K. Fong, J. D. Minna, and J. A. Roth Induction of Apoptosis and Inhibition of Tumorigenicity and Tumor Growth by Adenovirus Vector-mediated Fragile Histidine Triad (FHIT) Gene Overexpression Cancer Res., July 1, 1999; 59(14): 3333 - 3339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sorio, A. Baron, S. Orlandini, G. Zamboni, P. Pederzoli, K. Huebner, and A. Scarpa The FHIT Gene Is Expressed in Pancreatic Ductular Cells and Is Altered in Pancreatic Cancers Cancer Res., March 1, 1999; 59(6): 1308 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. T. Lynch, M. J. Casey, T. G. Shaw, and J. F. Lynch Hereditary Factors in Gynecologic Cancer Oncologist, October 1, 1998; 3(5): 319 - 338. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Pekarsky, M. Campiglio, Z. Siprashvili, T. Druck, Y. Sedkov, S. Tillib, A. Draganescu, P. Wermuth, J. H. Rothman, K. Huebner, et al. Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans PNAS, July 21, 1998; 95(15): 8744 - 8749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Pace, P. N. Garrison, A. K. Robinson, L. D. Barnes, A. Draganescu, A. Rosler, G. M. Blackburn, Z. Siprashvili, C. M. Croce, K. Huebner, et al. Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit PNAS, May 12, 1998; 95(10): 5484 - 5489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Inoue, H. Ishii, H. Alder, E. Snyder, T. Druck, K. Huebner, and C. M. Croce Sequence of the FRA3B common fragile region: Implications for the mechanism of FHIT deletion PNAS, December 23, 1997; 94(26): 14584 - 14589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Y. Y. Fong, V. Fidanza, N. Zanesi, L. F. Lock, L. D. Siracusa, R. Mancini, Z. Siprashvili, M. Ottey, S. E. Martin, T. Druck, et al. Muir-Torre-like syndrome in Fhit-deficient mice PNAS, April 25, 2000; 97(9): 4742 - 4747. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
