HOX GENE-EXPRESSION IN HUMAN SMALL-CELL LUNG CANCERS XENOGRAFTED INTONUDE-MICE

Transcription factors are crucial to an understanding of the molecular basis of neoplasia. Homeobox-containing genes are a family of transcr iptional regulators encoding DNA-binding homeodomains, involved in the control of normal development. Class-1 human chromosomal organization , perhaps directly related to their function. Aberrant expression of h omeobox-genes has been associated with both morphological abnormalitie s and oncogenesis. We have recently observed that alterations in HOX g ene expression are detectable in kidney and colon cancer when compared to the corresponding normal organs. Here we have analyzed the express ion of HOX genes in primary and metastatic human small-cell lung cance r (SCLC) xenografted in nude mice, in order to investigate whether HOX gene expression correlates with the histology and stage of SCLC progr ession. The results show that different SCLCs display differential pat terns of HOX gene expression. Furthermore, in SCLC, the number of acti vely expressed HOX genes might be substantially lower in metastatic ca ncers than in primary tumors. The alteration in HOX gene expression in SCLCs mainly concerns the HOX B and C loci. This finding suggests tha t downregulation of HOX genes may play a role in small-cell lung cance r progression, possibly through their implication in tumor suppression . (C) 1994 Wiley-Liss, Inc.