Early expression of the Helicase-Like Transcription Factor (HLTF/SMARCA3) in an experimental model of estrogen-induced renal carcinogenesis

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.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.The human helicase-like transcription factor (HLTF; SMARCA3 in OMIM) presents a RING-finger motif as well as the 7 DNA helicase domains characterizing the SWI/SNF family of chromatin remodeling factors [1]. Albeit devoid of helicase activity on naked DNA, these proteins are DNA-dependent ATPases that modify chromatin structure. SWI/SNF proteins displace nucleosomes on DNA by the propagation of a DNA bulge, i.e. a local distortion of the DNA double helix wrapped around the histone core (reviewed by [2]). SWI/SNF proteins were initially identified in yeast by the fact that their inactivation caused a global alteration of gene transcription. Some SWI/SNF proteins have been implicated in cellular functions so diverse as chromosome segregation (lodestar; [3]), nucleotide excision repair (RAD4, ERCC6, and RAD16; e.g. [4]), nucleosome reassembly after replication (I-SWI; [5]) and DNA double-strand break repair [6]. However, they have been mostly studied for their involvement in the regulation of transcription, where they act as large multiunit complexes (such as RSC, NURF, CHRAC, NURD...; reviewed in [7]).Most members of