Molecular Regulation of Androgen Receptors in Major Female Reproductive System Cancers

Int J Mol Sci. 2022 Jul 8;23(14):7556. doi: 10.3390/ijms23147556.

Abstract

There are three main types of cancer in the female reproductive system, specifically ovarian cancer (OVCA), endometrial cancer (EC), and cervical cancer (CC). They are common malignant tumors in women worldwide, with high morbidity and mortality. In recent years, androgen receptors (ARs) have been found to be closely related to the occurrence, progression, prognosis, and drug resistance of these three types of tumors. This paper summarizes current views on the role of AR in female reproductive system cancer, the associations between female reproductive system cancers and AR expression and polymorphisms. AR regulates the downstream target genes transcriptional activity and the expression via interacting with coactivators/corepressors and upstream/downstream regulators and through the gene transcription mechanism of "classical A/AR signaling" or "non-classical AR signaling", involving a large number of regulatory factors and signaling pathways. ARs take part in the processes of cancer cell proliferation, migration/invasion, cancer cell stemness, and chemotherapeutic drug resistance. These findings suggest that the AR and related regulators could target the treatment of female reproductive system cancer.

Keywords: androgen; androgen receptor; cervical cancer; endometrial carcinoma; ovarian cancer.

Publication types

  • Review

MeSH terms

  • Androgens / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Receptors, Androgen* / metabolism

Substances

  • Androgens
  • Receptors, Androgen

Grants and funding

This work was supported by Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Natural Science Foundation of China (32072722, 32072721), National Transgenic Creature Breeding Grand Project (2016zx08008-003) and Basic Research Project of Shanxi (20210302124640).