This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xiao, G. H. Articles by Yeung, R. S. Search for Related Content PubMed PubMed Citation Articles by Xiao, G. H. Articles by Yeung, R. S.

American Journal of Pathology, Vol 151, 1541-1547, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

The FHIT gene product is highly expressed in the cytoplasm of renal tubular epithelium and is down-regulated in kidney cancers

GH Xiao, F Jin, AJ Klein-Szanto, TL Goodrow, MW Linehan and RS Yeung
Division of Medical Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

Loss of heterozygosity and homozygous deletion of the 3p14.2 region in human cancers implies the existence of a tumor suppressor gene. One such candidate is the fragile histidine triad (FHIT) gene. To investigate the role of FHIT gene product in tumorigenesis, we generated specific polyclonal antibodies to the human protein and studied its expression in normal and tumor tissues. Immunoblot analysis revealed highly variable expression of pFhit in normal adult human tissues. The highest steady-state level of pFhit was found in kidney and brain, whereas breast, intestine, and skeletal muscle expressed only trace amounts. Within the kidney, the pattern of pFhit immunoreactivity was confined to the tubular epithelium and absent in the glomeruli. Immunofluorescence analysis and biochemical fractionation have sublocalized pFhit to the cytosolic compartment. Compared with normal kidney, pFhit was found to be down-regulated in a subset of primary renal cell carcinoma. Two of 12 renal cell carcinoma cell lines that are known not to contain VHL mutations showed complete loss of pFhit expression. This is supported by the appearance of aberrant reverse transcription-polymerase chain reaction products and loss of the normal-size fragment. Our results are consistent with a potential role of pFhit loss or dysfunction in human renal cell carcinoma independent of VHL involvement.

This article has been cited by other articles:

				K. Uematsu, A. Yoshimura, A. Gemma, H. Mochimaru, Y. Hosoya, S. Kunugi, K. Matsuda, M. Seike, F. Kurimoto, K. Takenaka, et al. Aberrations in the Fragile Histidine Triad (FHIT) Gene in Idiopathic Pulmonary Fibrosis Cancer Res., December 1, 2001; 61(23): 8527 - 8533. [Abstract] [Full Text] [PDF]

				X. P. Hao, J. E. Willis, T. G. Pretlow, J. S. Rao, G. T. MacLennan, I. C. Talbot, and T. P. Pretlow Loss of Fragile Histidine Triad Expression in Colorectal Carcinomas and Premalignant Lesions Cancer Res., January 1, 2000; 60(1): 18 - 21. [Abstract] [Full Text]

				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]

				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]