Progesterone Receptor is a Haploinsufficient Tumor Suppressor Gene in Cervical Cancer
| Autor: | Yuri Park, Chin-Yo Lin, Charles Ho, Seunghan Baik, Sang-Hyuk Chung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Genetically modified mouse
Cancer Research endocrine system Tumor suppressor gene Estrogen receptor Uterine Cervical Neoplasms 030209 endocrinology & metabolism Mice Transgenic Biology Article 03 medical and health sciences Mice 0302 clinical medicine Progesterone receptor medicine Animals Humans Genes Tumor Suppressor Allele skin and connective tissue diseases Molecular Biology Survival rate Cervical cancer medicine.disease Oncology 030220 oncology & carcinogenesis Cancer research Papilloma Female Receptors Progesterone hormones hormone substitutes and hormone antagonists |
| Zdroj: | Mol Cancer Res |
| Popis: | Tumor-suppressor genes (TSG) are often deleted or transcriptionally suppressed in cancer. PGR codes for progesterone receptor (PR), a transcription factor whose function depends on its ligand. Although PR expression is often undetectable in cervical cancer, its relevance to the endocrine-related etiology of this prevalent gynecological disease remains unclear. In this study, we show that the deletion of one Pgr allele in cervical epithelium promoted spontaneous cervical cancer in human papilloma viral oncogene-expressing transgenic mice as efficiently as the ablation of both Pgr alleles. We also show that tumors arising in the transgenic mice with one or both Pgr alleles did not express PR or expressed at the reduced levels compared with the normal epithelium. PR status correlated with estrogen receptor α (ERα) status in the mouse model and the Cancer Genome Atlas (TCGA) dataset. TCGA data analyses revealed that PGR expression significantly decreased in cervical cancer and that the biallelic deletion of PGR was rare. Furthermore, low PGR expression was associated with poor prognosis in young patients with cervical cancer. These discoveries point to PGR as a haploinsufficient TSG in the uterine cervix. They also raise the possibility that the restoration of PGR expression may improve the survival rate. Implications: The decreased expression of PR may increase the risk of cervical cancer in human papillomavirus–infected women. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/19/1/42/F1.large.jpg. |
| Databáze: | OpenAIRE |
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