Cited by 57Estrogen and related hormone effectsBreast Cancer Treatment StudiesCancer-related Molecular Pathways

Androgen receptor-induced tumor suppressor, KLLN, inhibits breast cancer growth and transcriptionally activates p53/p73-mediated apoptosis in breast carcinomas

Wang, Yu, He, Xin, Yu, Qi, Eng, Charis·2013·Human Molecular Genetics

Abstract

Androgen receptor (AR) expression by immunohistochemistry correlates with better prognosis and survival among breast cancer patients. We and others have shown that AR inhibits proliferation and induces apoptosis in breast cancer cells. However, the mechanism of AR's anti-tumor effect in breast cancer is still not fully understood. Our recent study indicates that AR upregulates expression of tumor suppressor gene PTEN by promoter activation in breast cancer. KLLN, encoding KLLN protein, is a newly identified gene, which shares a bidirectional promoter with PTEN and is transcribed in the opposite direction. So far, the function of KLLN has never been studied in tumorigenesis. Here, we define KLLN as a tumor suppressor in breast carcinomas, which inhibits tumor growth and invasiveness. After analyzing 188 normal breast and 1247 malignant breast cancer tissues, we observed the loss of KLLN in multiple breast cancer subtypes and this decreased KLLN expression associates with tumor progression and increasing histological grade in invasive carcinomas. We characterize KLLN, for the first time, as a transcription factor, directly promoting the expression of TP53 and TP73, with consequent elevated apoptosis and cell cycle arrest in breast cancer cells. We demonstrate, in vitro and in murine xenograph models, that both KLLN and PTEN are AR-target genes, mediating androgen-induced growth inhibition and apoptosis in breast cancer cells. Our observations suggest that KLLN might be used as a potential prognostic marker and novel therapy target for breast carcinomas.

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Crossref · 10.1093/hmg/ddt077

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  • Hypermethylation of MGMT has been reported to decrease apoptotic responses to DNA damage by TP73 and cell proliferation regulation by RBBP7, which in combination with aberrant expression of HOXA10, increase susceptibility for endometriosis.

    “The hypermethylation of methyltransferase (MGMT) has been reported to decrease apoptotic responses to DNA damage by TP73 and cell proliferation regulation by RBBP7, which in combination with the aberrant expression of HOXA10, increase the susceptibility for endometriosis.12,[41][42][43][44][45][46][47][48]”

    From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [41]

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Authors
Wang, Y., He, X., Yu, Q., & Eng, C.
Affiliations
Cleveland Clinic (US)
Corresponding author
Eng, Charis
Venue
Human Molecular Genetics
Published
2013-02-14
Volume
22
Issue
11
Pages
2263-2272
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W2151584857
Cited by
57
References
37
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 3
FWCI
3.76
Type
journal article
Language
en
Open access
closed
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
androgen receptor, breast cancer, tumor suppressor, PTEN, bidirectional promoter, p53, p73, apoptosis, cell cycle arrest, tumor progression, prognostic factors, tumor invasion
MeSH terms
Tumor Protein p73, Aged, Androgens, Animals, Breast Neoplasms, Carcinoma, DNA-Binding Proteins, Female, Humans, Middle Aged, Nuclear Proteins, Receptors, Androgen, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Apoptosis, Tumor Suppressor Proteins, Cell Line, Tumor, Mice, Neoplasm Grading

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