Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract.
Although epithelial ovarian cancers (EOCs) have been thought to arise from the simple epithelium lining the ovarian surface or inclusion cysts, the major subtypes of EOCs show morphologic features that resemble those of the müllerian duct-derived epithelia of the reproductive tract. We found that HOX genes, which normally regulate mullerian duct differentiation, are not expressed in normal ovarian surface epithelium (OSE), but are expressed in different EOC subtypes according to the pattern of mullerian-like differentiation of these cancers. Ectopic expression of Hoxa9 in tumorigenic mouse OSE cells gave rise to papillary tumors resembling serous EOCs. In contrast, Hoxa10 and Hoxa11 induced morphogenesis of endometrioid-like and mucinous-like EOCs, respectively. Hoxa7 showed no lineage specificity, but promoted the abilities of Hoxa9, Hoxa10 and Hoxa11 to induce differentiation along their respective pathways. Therefore, inappropriate activation of a molecular program that controls patterning of the reproductive tract could explain the morphologic heterogeneity of EOCs and their assumption of müllerian-like features.
Cheng
Wenjun
W
Department of Molecular Therapeutics, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 184, Houston, Texas 77030, USA.
Liu
Jinsong
J
Yoshida
Hiroyuki
H
Rosen
Daniel
D
Naora
Honami
H
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009095:Mullerian Ducts / Q000166:cytology / Q000502:physiology*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; D018398:Homeodomain Proteins