Fragile histidine triad gene expression in primary prostate cancer and in an in vitro model.
BACKGROUND
The fragile histidine triad (FHIT) is frequently deleted and altered in many human cancers. Replacement of the FHIT gene into cancer cell lines lacking FHIT expression results in loss of tumorigenicity and tumor growth.


METHODS
We investigated the status and function of the FHIT gene in the etiology of prostate carcinoma, utilizing human prostate cancer tissues and cell lines and the multistep human prostate epithelial (HPE) cell tumor model.


RESULTS
In primary cancers, either no FHIT protein expression or greatly reduced expression was observed in the tumor cells, while FHIT was expressed at high levels in the adjacent normal prostate epithelia. No aberrant FHIT transcripts were observed in normal HPE cells. Aberrant transcripts were observed in the immortalized and nontumorigenic HPV-18 C-1 cell line. A tumor cell line (129 Nu 5002-1) derived from chemical transformation of HPV-18 C-1 cells did not express the FHIT gene. Immunoblot analysis of FHIT protein levels confirmed the absence of FHIT expression in the 129 Nu 5002-1 tumor cell line. Among the metastatic prostate cancer cell lines, PC-3, DU-145, and S7 exhibited aberrant transcripts, but the LNCaP cell line (early passage) was normal. Upon cloning of the cDNA and determining the DNA sequence of the PCR fragments, we observed specific alterations such as deletions and insertions in the aberrant transcripts. A majority of prostate cancer cell lines expressed the normal-sized transcript in addition to the aberrant transcripts.


CONCLUSIONS
Our results indicate that alterations in the FHIT gene represent an early event in prostate carcinogenesis.
Guo
Z
Z
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-4525, USA.
Johansson
S L
SL
Rhim
J S
JS
Vishwanatha
J K
JK
D017766:Acid Anhydride Hydrolases; D001483:Base Sequence / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase