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Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis

Nature Reviews Cancer volume 6, pages 360–368 (2006)Cite this article

Key Points

  • Endometrial cancer is the most common gynaecological malignancy.

  • Although no specific gene or genes have been linked to the majority of cases of endometrial cancer, several well-characterized oncogenes and tumour-suppressor genes have been implicated in endometrial carcinogenesis.

  • Approximately 80% of endometrial cancer cases are type I tumours, which are usually well differentiated and endometrioid in histology, and are associated with a history of unopposed oestrogen exposure or other hyperoestrogenic risk factors such as obesity.

  • Oestrogen and selective oestrogen-receptor modulators (SERMs) are implicated in endometrial carcinogenesis through regulation of gene transcription.

  • Oestrogen and SERMs exert their carcinogenic roles in the endometrium through their downstream molecular effectors such as PAX2 (paired box gene 2).

Abstract

Endometrial cancer is the most common gynaecological cancer, and is associated with endometrial hyperplasia, unopposed oestrogen exposure and adjuvant therapy for breast cancer using selective oestrogen-receptor modulators (SERMs), particularly tamoxifen. Oestrogen and SERMs are thought to be involved in endometrial carcinogenesis through their effects on transcriptional regulation. Ultimately, oestrogen and SERMs affect the transduction of cellular signalling pathways that govern cell growth and proliferation, through downstream effectors such as PAX2 (paired box 2).

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Figure 1: Genomic action of oestrogen and tamoxifen in the uterus.
Figure 2: PAX2 in the endometrium.

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Acknowledgements

Work in laboratory of Y.S. was supported by grants from the National Natural Science Foundation of China and by the '863 Program' and the '973 Program' of the Ministry of Science and Technology of China.

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  1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, 100083, China

    Yongfeng Shang

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DATABASES

National Cancer Institute

breast cancer

endometrial cancer

Wilms' tumour

FURTHER INFORMATION

Breast Cancer Prevention Trial

National Surgical Adjuvant Breast and Bowel Project

The Study of Tamoxifen and Raloxifene

United States National Toxicology Program listed steroidal oestrogens as carcinogens (2002)

Glossary

Endometrioid

A tumour containing epithelial or stromal elements resembling endometrial tissue.

SERMs

A group of chemical compounds that are structurally related to oestrogens, biochemically bind to oestrogen receptors, and functionally exert different effects on different tissues.

Second-, third- and fourth-generation SERMs

Chemical compounds that are developed in different stages and are intended to improve the beneficial effects and reduce the harmful effects of original SERMs.

Genotoxicity

Effects that cause genetic mutations and/or changes in chromosome structure and number.

Canonical

Standard or well-established and recognized DNA sequences to which transcription factors bind.

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Shang, Y. Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis. Nat Rev Cancer 6, 360–368 (2006). https://doi.org/10.1038/nrc1879

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