Tiberio C, Barba P, Magli M C, Arvelo F, Le Chevalier T, Poupon M F, Cillo C
International Institute of Genetics and Biophysics, Naples, Italy.
Int J Cancer. 1994 Aug 15;58(4):608-15. doi: 10.1002/ijc.2910580426.
Transcription factors are crucial to an understanding of the molecular basis of neoplasia. Homeobox-containing genes are a family of transcriptional regulators encoding DNA-binding homeodomains, involved in the control of normal development. Class-I human homeobox-containing genes (HOX genes) display a peculiar chromosomal organization, perhaps directly related to their function. Aberrant expression of homeobox-genes has been associated with both morphological abnormalities and oncogenesis. We have recently observed that alterations in HOX gene expression are detectable in kidney and colon cancer when compared to the corresponding normal organs. Here we have analyzed the expression of HOX genes in primary and metastatic human small-cell lung cancer (SCLC) xenografted in nude mice, in order to investigate whether HOX gene expression correlates with the histology and stage of SCLC progression. The results show that different SCLCs display differential patterns of HOX gene expression. Furthermore, in SCLC, the number of actively expressed HOX genes might be substantially lower in metastatic cancers than in primary tumors. The alteration in HOX gene expression in SCLCs mainly concerns the HOX B and C loci. This finding suggests that downregulation of HOX genes may play a role in small-cell lung cancer progression, possibly through their implication in tumor suppression.
转录因子对于理解肿瘤形成的分子基础至关重要。含同源框的基因是一类转录调节因子家族，编码参与正常发育调控的DNA结合同源结构域。I类含人类同源框的基因（HOX基因）呈现出一种特殊的染色体组织形式，可能与其功能直接相关。同源框基因的异常表达与形态学异常和肿瘤发生均有关联。我们最近观察到，与相应的正常器官相比，在肾癌和结肠癌中可检测到HOX基因表达的改变。在此，我们分析了移植到裸鼠体内的原发性和转移性人类小细胞肺癌（SCLC）中HOX基因的表达情况，以研究HOX基因表达是否与SCLC进展的组织学和分期相关。结果表明，不同的SCLC呈现出HOX基因表达的差异模式。此外，在SCLC中，转移性癌中活跃表达的HOX基因数量可能比原发性肿瘤中的要低得多。SCLC中HOX基因表达的改变主要涉及HOX B和C位点。这一发现表明，HOX基因的下调可能在小细胞肺癌进展中发挥作用，可能是通过其在肿瘤抑制中的作用实现的。
