Loss of function of the tissue specific transcription factor HNF1 alpha in renal cell carcinoma and clinical prognosis.
BACKGROUND
Human renal cell carcinogenesis is associated with loss of expression of tissue-specific genes and loss of function of tissue-specific transcription factors such as HNF(hepatic nuclear factor)1 alpha.


METHODS
In this study HNF1 alpha DNA-binding activities and protein amounts were determined by gel retardation assay and Western blot analysis, respectively, in 42 non-metastasized renal cell carcinomas and paired normal tissues.


RESULTS
36 tumors out of 42 (86%) showed diminished binding activity of HNF1 alpha. In most cases (26 out of 42) this appeared to be due to decreased amounts of HNF1 alpha protein, but 10 tumors contained equal or even higher amounts of HNF1 alpha, in spite of reduced binding to DNA. Only 6 tumors out of 42 had unaltered HNF1 alpha binding activity. A clinical follow-up was obtained for 40 patients. Over an average follow-up period of 39 months no significant differences in the survival rate were observed between patients having lost or retained HNF1 alpha function. However, since most of the patients with retained function are still alive, long-term follow-up might be warranted.


CONCLUSIONS
The very high incidence of loss of HNF1 alpha function indicates the important biological role of this change in renal cell carcinoma.
Anastasiadis
A G
AG
Department of Urology, Heinrich-Heine-University, Düsseldorf, Germany. anastasi@uni-duesseldorf.de
Lemm
I
I
Radzewitz
A
A
Lingott
A
A
Ebert
T
T
Ackermann
R
R
Ryffel
G U
GU
Schulz
W A
WA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics; D009687:Nuclear Proteins; D011379:Prognosis; D011485:Protein Binding; D015996:Survival Rate; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D004247:DNA