Progesterone: the ultimate endometrial tumor suppressor - PubMed (original) (raw)
Review
Progesterone: the ultimate endometrial tumor suppressor
Shujie Yang et al. Trends Endocrinol Metab. 2011 Apr.
Abstract
The uterine endometrium is exquisitely sensitive to steroid hormones that act through well-described nuclear receptors. Estrogen drives epithelial proliferation, and progesterone inhibits growth and causes cell differentiation. The importance of progesterone as a key inhibitor of carcinogenesis is reflected by the observation that women who ovulate and produce progesterone almost never get endometrial cancer. In this review we describe seminal research findings that define progesterone as the major endometrial tumor suppressor. We discuss the genes and diverse signaling pathways that are controlled by progesterone through progesterone receptors (PRs) and also the multiple factors that regulate progesterone/PR activity. By defining these progesterone-regulated factors and pathways we identify the principal therapeutic opportunities to control the growth of endometrial cancer.
Copyright © 2011. Published by Elsevier Ltd.
Figures
Figure 1
Progesterone receptor structural elements. Diagrammed are the two primary human isoforms of progesterone receptor, PRA and PRB. PRB contains an extra 164 amino acids at the N-terminus. Within this region is AF-3, which is unique to PRB. AF, activation function; DBD, DNA-binding domain; LBD, ligand-binding domain.
Figure 2
Progesterone web of influence. Through genomic and non-genomic regulation, progesterone acts as a tumor suppressor to promote (➞) apoptosis, differentiation, and cell cycle arrest, and to inhibit (
) inflammation and invasion.
Similar articles
- Role of progesterone in endometrial cancer.
Kim JJ, Chapman-Davis E. Kim JJ, et al. Semin Reprod Med. 2010 Jan;28(1):81-90. doi: 10.1055/s-0029-1242998. Epub 2010 Jan 26. Semin Reprod Med. 2010. PMID: 20104432 Free PMC article. Review. - Role of nuclear progesterone receptor isoforms in uterine pathophysiology.
Patel B, Elguero S, Thakore S, Dahoud W, Bedaiwy M, Mesiano S. Patel B, et al. Hum Reprod Update. 2015 Mar-Apr;21(2):155-73. doi: 10.1093/humupd/dmu056. Epub 2014 Nov 18. Hum Reprod Update. 2015. PMID: 25406186 Free PMC article. Review. - Progesterone receptor action in leiomyoma and endometrial cancer.
Kim JJ, Sefton EC, Bulun SE. Kim JJ, et al. Prog Mol Biol Transl Sci. 2009;87:53-85. doi: 10.1016/S1877-1173(09)87002-6. Epub 2009 Oct 7. Prog Mol Biol Transl Sci. 2009. PMID: 20374701 Free PMC article. Review. - Critical tumor suppressor function mediated by epithelial Mig-6 in endometrial cancer.
Kim TH, Lee DK, Cho SN, Orvis GD, Behringer RR, Lydon JP, Ku BJ, McCampbell AS, Broaddus RR, Jeong JW. Kim TH, et al. Cancer Res. 2013 Aug 15;73(16):5090-9. doi: 10.1158/0008-5472.CAN-13-0241. Epub 2013 Jun 27. Cancer Res. 2013. PMID: 23811943 Free PMC article. - [Clinical significance of analysis of estrogen and progesterone receptors in human uterine tissues].
Maleeva A, Milkov V. Maleeva A, et al. Akush Ginekol (Mosk). 1991 May;(5):55-7. Akush Ginekol (Mosk). 1991. PMID: 1897675 Russian.
Cited by
- Novel perspectives on the link between obesity and cancer risk: from mechanisms to clinical implications.
Shi X, Jiang A, Qiu Z, Lin A, Liu Z, Zhu L, Mou W, Cheng Q, Zhang J, Miao K, Luo P. Shi X, et al. Front Med. 2024 Nov 14. doi: 10.1007/s11684-024-1094-2. Online ahead of print. Front Med. 2024. PMID: 39542988 Review. - Metformin for endometrial hyperplasia.
Shiwani H, Clement NS, Daniels JP, Atiomo W. Shiwani H, et al. Cochrane Database Syst Rev. 2024 May 2;5(5):CD012214. doi: 10.1002/14651858.CD012214.pub3. Cochrane Database Syst Rev. 2024. PMID: 38695827 Review. - Diagnostic and therapeutic use of oral micronized progesterone in endocrinology.
Memi E, Pavli P, Papagianni M, Vrachnis N, Mastorakos G. Memi E, et al. Rev Endocr Metab Disord. 2024 Aug;25(4):751-772. doi: 10.1007/s11154-024-09882-0. Epub 2024 Apr 23. Rev Endocr Metab Disord. 2024. PMID: 38652231 Free PMC article. Review. - TSLP enhances progestin response in endometrial cancer via androgen receptor signal pathway.
Lv M, Xu Y, Chen P, Li J, Qin Z, Huang B, Liu Y, Tao X, Xiang J, Wang Y, Feng Y, Zheng W, Zhang Z, Li L, Liao H. Lv M, et al. Br J Cancer. 2024 Mar;130(4):585-596. doi: 10.1038/s41416-023-02545-y. Epub 2024 Jan 3. Br J Cancer. 2024. PMID: 38172534 - Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.
Thiel KW, Newtson AM, Devor EJ, Zhang Y, Malmrose PK, Bi J, Losh HA, Davies S, Smith LE, Padilla J, Leiva SM, Grueter CE, Breheny P, Hagan CR, Pufall MA, Gertz J, Guo Y, Leslie KK. Thiel KW, et al. J Steroid Biochem Mol Biol. 2023 Nov;234:106399. doi: 10.1016/j.jsbmb.2023.106399. Epub 2023 Sep 15. J Steroid Biochem Mol Biol. 2023. PMID: 37716459 Free PMC article.
References
- Huet-Hudson YM, et al. Estrogen regulates the synthesis of epidermal growth factor in mouse uterine epithelial cells. Mol Endocrinol. 1990;4:510–523. - PubMed
- Lingham RB, et al. Estrogen regulation of epidermal growth factor receptor messenger ribonucleic acid. Mol Endocrinol. 1988;2:230–235. - PubMed
- Murphy LJ, et al. Estrogen induces insulin-like growth factor-I expression in the rat uterus. Mol Endocrinol. 1987;1:445–450. - PubMed
- Weisz A, Bresciani F. Estrogen induces expression of c-fos and c-myc protooncogenes in rat uterus. Mol Endocrinol. 1988;2:816–824. - PubMed
- Guo RX, et al. 17 beta-estradiol activates PI3K/Akt signaling pathway by estrogen receptor (ER)-dependent and ER-independent mechanisms in endometrial cancer cells. J Steroid Biochem Mol Biol. 2006;99:9–18. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials