El cáncer cervicouterino (CaCU) es una enfermedad multifactorial que se asocia a factores genéticos, ambientales y epigenéticos, y cuyo principal agente etiológico es la infección por el virus del papiloma humano. Además, la alteración en la expresión de factores de transcripción ha sido considerada de importancia para el desarrollo de esta neoplasia. Los genes HOX codifican un grupo de factores de transcripción que participan en los procesos de proliferación y diferenciación celular durante el desarrollo de las estructuras embrionarias en los vertebrados; y su expresión aberrante ha sido asociada con oncogénesis y metástasis. Una serie de evidencias sugiere un papel importante para los genes HOX en el desarrollo neoplásico de la célula cervical. Estudios realizados en líneas celulares de CaCU, lesiones premalignas y tumores primarios han sugerido el involucramiento de HOXA1, HOXC5, C6, C8 y C10, HOXD9 y HOXD13 en el proceso de carcinogénesis cervical. Asimismo, la expresión de novo de los genes HOXB2, B4, B13 y HOXC11-C13 parece estar involucrada en el proceso de transformación maligna de la célula del epitelio cervical. Estos datos permitirían abrir un campo en la búsqueda de nuevos marcadores moleculares en cáncer cervical y en el desarrollo de nuevas estrategias terapéuticas para atender esta neoplasia.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74-108.
Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55(4):244-65.
Coletta P, Shimeld S y Sharpe P. The molecular anatomy of Hox gene expression. J Anat. 1994;189(Pt 1):15-22.
McGinnis W y Krumlauf R. Homeobox genes and axial patterning. Cell. 1992;68(2):283-302.
Mark M, Rijli FM, Chambon P. Homeobox genes in embryogenesis and pathogenesis. Pediatr Res. 1997; 42(4):421-9.
Akam M. Hox and HOM: homologous gene clusters in insects and vertebrates. Cell. 1989;57(3):347-9.
Krumlauf R. Hox genes in vertebrate development. Cell. 1994;78(2):191-201.
Gehring WJ, Qian YQ, Billeter M, Furukubo-Tokunaga K, Schier AF, Resendez-Perez D, et al. Homeodomain-DNA recognition. Cell. 1994;78(2): 211-23.
Garcia-Fernández J. The genesis and evolution of homeobox gene clusters. Nat Rev Genet. 2005;6(12):881-92.
Scott MP. Vertebrate homeobox gene nomenclature. Cell. 1992;71(4):551-3.
Apiou F, Flagiello D, Cillo C, Malfay B, Poupon M y Dutrillaux B. Fine mapping of human HOX gene cluster. Cytogenet Cell Genet. 1996;73(1-2):114-5.
Ferrier DE, Holland PW. Ancient origin of the HOX gene cluster. Nature. 2001;2(1):33-8.
Veraksa A, Del Campo M, McGinnis W. Developmental patterning genes and their conserved functions: from model organisms to humans. Mol Genet Metab. 2000;69(2):85-100.
Abate-Shen C. Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer. 2002;2(10):777-85.
Cantile M, Franco R, Tschan A, Baumhoer D, Zoblec I, Schiavo G, et al. HOXD13 expression across 79 tumor tissue types. Int J Cancer. 2009;125(7):1532-41.
Stuart E, Yokota Y, Gruss P. PAX and HOX in neoplasia. Adv Genet. 1994;33:255-74.
Taylor HS, Vanden GB and Igarashi P. A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod. 1997;57(6):1338-45.
Taylor HS, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998;101(7):1379-84.
Cermik D, Karaca M, Taylor HS. HOXA10 expression is repressed by progesterone in the myometrium: differential tissue-specific regulation of HOX gene expression in the reproductive tract. J Clin Endocrinol Metabol. 2001;86(7):3387-92.
Taylor HS, Igarashi P, Olive DL, Arici A. Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metabol. 1999;84(3):1129-35.
Ma L, Benson GV, Lim H, Dey SK, Mass RL. Abdominal B (AbdB) Hoxa genes: regulation in adult uterus by estrogen and progesterone and repression in Müllerian duct by the synthetic estrogen diethylstilbestrol (DES). Dev Biol. 1998;197(2):141-54.
Satokata I, Benson G, Mass R. Sexually dimorphic sterility phenotypes in Hoxa10 deficient mice. Nature. 1995;374(6521):460-3.
Gendron RL, Paradis H, Hsieh-Li HM, Lee DW, Potter SS, Markoff E. Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice. Biol Reprod. 1997;56(5):1097-105.
Mortlock DP, Innis JW. Mutation of HOXA13 in hand-foot-genital syndrome. Nature Genet. 1997;15(2):179-80.
Li H, Huang CJ, Choo KB. Expression of homeobox genes in cervical cáncer. Gynecol Oncol. 2002;84(2):216-21.
Alami Y, Castronovo V, Belotti D, Flagiello D, Clausse N. HOXC5 and HOXC8 expression are selectively turned on in human cervical cancer cell compared to normal keratinocytes. Biochem Biophys Res Commun. 1999;257(3):738-45.
Hung YC, Ueda M, Terai Y, Kumagai K, Ueki K, Kanda K, et al. Homeobox gene expression and mutation in cervical carcinoma cells. Cancer Sci. 2003;94(5):437-41.
Shim C, Zhang W. Hun C, Lee J-H. Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array. Clin Cancer Res. 1998;4(12):3045-50.
Santin AD, Zhan F, Bignotti E, Siegel ER, Cané S, Bellone S, et al. Gene expression profiles of primary HPV16- and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy. Virology. 2005;331(2):269-91.
López R, Garrido E, Vázquez G, Piña P, Pérez C, Alvarado I, et al. A subgroup of HOX Abd-B gene is differentially expressed in cervical cancer. Int J Gynecol Cancer. 2006;16(3):1289-96.
López R, Garrido E, Piña P, Hidalgo A, Lazos M, Ochoa R, et al. HOXB homeobox gene expression in cervical carcinoma. Int J Gynecol Cancer. 2006;16(1):329-35.
Barba-de la Rosa AP, Briones-Cerecero E, Lugo-Melchor O, De León-Rodríguez A, Santos L, Castelo-Ruelas J, et al. Hox B4 as potential marker of non-differentiated cells in human cervical cancer cells. J Cancer Res Clin Oncol. 2012;138(2):293-300. doi: 10.1007/s00432-011-1081-2. Epub 2011 Nov 27.
Tomotsume D, Shoji H, Wakamatsu Y, Kondosh H, Takahashi N. A mouse homologue of the Drosophila tumor-suppressor gene l(2)gl controlled by Hox-C8 in vivo. Nature. 1993;365(6441):69-72.
Zhai Y, Kuick R, Nan B, Ota I, Weiss SJ, Trimble CL, et al. Gene expression analysis of preinvasive and invasive cervical squamous cell carcinomas identifies HOXC10 as a key mediator of invasion. Cancer Res. 2007;67(21):10163-72.
How C, Hui AB, Alajez NM, Shi W, Boutros PC, Clarke BA, et al. MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. PLoS One. 2013;8(7):e67846.