HOXC5 and HOXC8 expression are selectively turned on in human cervical cancer cells compared to normal keratinocytes.

A growing number of data have sustained the involvement of homeobox genes expression deregulation in cancer. In this study, we have performed an exhaustive survey of the expression of the 39 class I HOX genes expressed in normal and malignant human cervix keratinocytes. Using RT-PCR, we observed that the vast majority (34/39) of HOX genes are expressed in normal keratinocytes. Only HOXA2, HOXA7, HOXC5, HOXC8 and HOXD12 were found to be silent. Interestingly, this pattern is conserved in the transformed keratinocytes (SiHa cells) except for the appearance of HOXC5 and HOXC8 mRNA. The HOXC5 and HOXC8 expression was also observed in two other transformed keratinocytes cell lines of independent origins, Eil-8 and 18-11S3, and confirmed by in situ hybridization. Our data add weight to the body of evidence attributing to a specific adult tissue a particular combination of expressed HOX genes and suggest that HOXC5 and/or HOXC8 could be involved in the process leading to the transformation of cervical keratinocytes.

[1]  F. Apiou,et al.  Fine mapping of human HOX gene clusters. , 1996, Cytogenetics and cell genetics.

[2]  L. Sachs,et al.  DNA rearrangement of a homeobox gene in myeloid leukaemic cells. , 1988, The EMBO journal.

[3]  S. Korsmeyer,et al.  Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. , 1991, Science.

[4]  A. Simeone,et al.  HOX gene activation by retinoic acid. , 1991, Trends in genetics : TIG.

[5]  M. Scott.  Vertebrate homeobox gene nomenclature , 1992, Cell.

[6]  William McGinnis,et al.  Homeobox genes and axial patterning , 1992, Cell.

[7]  C. Meijer,et al.  HOXC4, HOXC5, and HOXC6 expression in non-Hodgkin's lymphoma: preferential expression of the HOXC5 gene in primary cutaneous anaplastic T-cell and oro-gastrointestinal tract mucosa-associated B-cell lymphomas. , 1997, Blood.

[8]  M. Levine,et al.  Homeobox proteins as sequence-specific transcription factors , 1988, Cell.

[9]  V. Castronovo,et al.  Homeobox genes: potential candidates for the transcriptional control of the transformed and invasive phenotype. , 1994, Biochemical pharmacology.

[10]  H. Kondoh,et al.  A mouse homologue of the Drosophila tumour-suppressor gene l(2)gl controlled by Hox-C8 in vivo , 1993, Nature.

[11]  M. D'Esposito,et al.  Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells , 1991, Mechanisms of Development.

[12]  Unnur Thorsteinsdottir,et al.  Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b , 1998, The EMBO journal.

[13]  D. Cheresh,et al.  Induction of the Angiogenic Phenotype by Hox D3 , 1997, The Journal of cell biology.

[14]  Y. Ito,et al.  Studies on a New Human Cell Line (SiHa) Derived from Carcinoma of Uterus. I. Its Establishment and Morphology 1 , 1970, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[15]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[16]  E. Boncinelli,et al.  HOX gene expression in normal and neoplastic human kidney , 1992, International journal of cancer.

[17]  C. Cillo.  HOX genes in human cancers. , 1994, Invasion & metastasis.

[18]  M. Akam.  Hox and HOM: Homologous gene clusters in insects and vertebrates , 1989, Cell.

[19]  M. Poupon,et al.  Hox gene expression in human small‐cell lung cancers xenografted into nude mice , 1994, International journal of cancer.

[20]  E. Boncinelli,et al.  Expression of homeobox-containing genes in primary and metastatic colorectal cancer. , 1993, European journal of cancer.

[21]  David Baltimore,et al.  A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B all , 1990, Cell.

[22]  A. Gown,et al.  Altered expression of proliferation and differentiation markers in human papillomavirus 16 and 18 immortalized epithelial cells grown in organotypic culture. , 1992, The American journal of pathology.

[23]  V. Castronovo,et al.  Expression and modulation of homeobox genes from cluster B in endothelial cells. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[24]  Michael L. Cleary,et al.  Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor , 1990, Cell.

[25]  M. Scott,et al.  The structure and function of the homeodomain. , 1989, Biochimica et biophysica acta.

[26]  A. Perkins,et al.  Homeobox gene expression plus autocrine growth factor production elicits myeloid leukemia. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Meijer,et al.  HOXC4, HOXC5, and HOXC6 expression in primary cutaneous lymphoid lesions. High expression of HOXC5 in anaplastic large-cell lymphomas. , 1997, The American journal of pathology.

[28]  F. M. Hack,et al.  Lineage-restricted expression of homeobox-containing genes in human hematopoietic cell lines. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[29]  E. Boncinelli,et al.  Coordinate regulation of HOX genes in human hematopoietic cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[30]  G. Morata,et al.  Colinearity and functional hierarchy among genes of the homeotic complexes. , 1994, Trends in genetics : TIG.

[31]  M. D'Esposito,et al.  The human HOX gene family. , 1989, Nucleic acids research.

[32]  J. Foidart,et al.  Immortalization of human cervical keratinocytes by human papillomavirus type 33 , 1993, International journal of cancer.

[33]  P Gruss,et al.  The oncogenic potential of deregulated homeobox genes. , 1993, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.