Early expression of the Helicase-Like Transcription Factor (HLTF/SMARCA3) in an experimental model of estrogen-induced renal carcinogenesis.
BACKGROUND
The Helicase-Like Transcription Factor (HLTF/SMARCA3) belongs to the family of SWI/SNF proteins that use the energy of ATP hydrolysis to remodel chromatin in a variety of cellular processes. Several SWI/SNF genes are disrupted in cancer, suggesting a role of tumor suppressor. Similarly, the HLTF gene was recently found to be inactivated by hypermethylation in a number of advanced colon and gastric tumors. However, other evidences indicated a 20-fold HLTF overexpression in cell lines derived from various neoplasms (ovary, breast, cervix, kidney...).


RESULTS
In the present study, we investigated HLTF expression by immunohistochemistry in a model of kidney tumors induced by continuous administration of diethylstilbestrol to male Syrian golden hamsters. A strong labeling was already detected in small tumor buds, making HLTF an early cancer marker in this model. Although every cell stained for HLTF at this early stage, the number of HLTF-positive cells decreased to 10% with cancer progression, and these positive cells were dispersed in the tumor mass. HLTF expression was conserved in the HKT-1097 cell line established from kidney tumors, but again only 10% of positive cells were found in xenografts produced by HKT-1097 cells in nude mice.


CONCLUSIONS
In conclusion, our data suggest that HLTF gene activation is linked to initial steps of carcinogenesis in this model and should be investigated in early stages of other neoplasms.
Debauve
Gaël
G
Laboratory of Molecular Biology, University of Mons-Hainaut, Mons, Belgium. gael.debauve@umh.ac.be
Nonclercq
Denis
D
Ribaucour
Fabrice
F
Wiedig
Murielle
M
Gerbaux
Cécile
C
Leo
Oberdan
O
Laurent
Guy
G
Journé
Fabrice
F
Belayew
Alexandra
A
Toubeau
Gérard
G
D000818:Animals; D001483:Base Sequence; D006224:Cricetinae; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000494:pharmacology; D018450:Disease Progression; D004967:Estrogens / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D004967:Estrogens; C100023:HLTF protein, human; D014157:Transcription Factors; D004054:Diethylstilbestrol; D004265:DNA Helicases