Sox9 overexpression in uterine epithelia induces endometrial gland hyperplasia.
SOX9 is a high mobility group transcription factor that is required in many biological processes, including cartilage differentiation, endoderm progenitor maintenance, hair differentiation, and testis determination. SOX9 has also been linked to colorectal, prostate, and lung cancer. We found that SOX9 is expressed in the epithelium of the adult mouse and human uterus, predominantly marking the uterine glands. To determine if SOX9 plays a role in the development of endometrial cancer we overexpressed Sox9 in the uterine epithelium using a progesterone receptor-Cre mouse model. Sox9 overexpression in the uterine epithelium led to the formation of simple and complex cystic glandular structures in the endometrium of aged-females. Histological analysis revealed that these structures appeared morphologically similar to structures present in patients with endometrial hyperplastic lesions and endometrial polyps that are thought to be precursors of endometrial cancer. The molecular mechanisms that cause the glandular epithelium to become hyperplastic, leading to endometrial cancer are still poorly understood. These findings indicate that chronic overexpression of Sox9 in the uterine epithelium can induce the development of endometrial hyperplastic lesions. Thus, SOX9 expression may be a factor in the formation of endometrial cancer.
Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Gabriel
G
Gonzalez
Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Shyamin
S
Mehra
Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Ying
Y
Wang
Department of Orthopedic Surgery, Gifu University, Gifu City 501-1194, Japan.
Haruhiko
H
Akiyama
Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rrb@mdanderson.org.
Richard R
RR
Behringer
D000818:Animals; D004714:Endometrial Hyperplasia / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000254:growth & development / Q000473:pathology; D004848:Epithelium / Q000254:growth & development / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D011980:Receptors, Progesterone / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology; D014599:Uterus / Q000378:metabolism* / Q000473:pathology
D011980:Receptors, Progesterone; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse
Cancer; Endometrium; Sox9; Transgenic mouse; Uterus