High tumoral levels of Kiss1 and G-protein-coupled receptor 54 expression are correlated with poor prognosis of estrogen receptor-positive breast tumors.
Marot. Didier D; Bieche. Ivan I; Aumas. Chantal C; Esselin. Stéphanie S; Bouquet. Céline C; Vacher. Sophie S; Lazennec. Gwendal G; Perricaudet. Michel M; Kuttenn. Frederique F; Lidereau. Rosette R; de Roux. Nicolas N
Key Findings
- Kiss1 is present in some breast cancer cell lines and its levels change with estrogen signaling.
- Tamoxifen raises Kiss1 and GPR54 levels in estrogen‑positive breast cancer cells.
- High tumor levels of Kiss1 and GPR54 predict shorter relapse‑free survival in tamoxifen‑treated, post‑menopausal, ER‑positive breast cancer patients.
Practical Outcomes
- For biohackers, the findings don’t translate into actionable protocols for longevity, metabolism, or performance. The data mainly suggest a potential biomarker for breast cancer drug resistance, not a supplement or intervention you can apply to yourself.
Summary
The study looked at a protein called kisspeptin (Kiss1) and its receptor GPR54 in breast cancer. It found that in estrogen‑positive tumors, higher levels of these molecules were linked to a worse outcome after tamoxifen treatment, suggesting they might signal resistance to the drug, but this doesn’t give any direct tips for everyday health or performance improvement.
Abstract
KiSS1 is a putative metastasis suppressor gene in melanoma and breast cancer-encoding kisspeptins, which are also described as neuroendocrine regulators of the gonadotropic axis. Negative as well as positive regulation of KiSS1 gene expression by estradiol (E(2)) has been reported in the hypothalamus. Estrogen receptor alpha (ERalpha level is recognized as a marker of breast cancer, raising the question of whether expression of KiSS1 and its G-protein-coupled receptor (GPR54) is down- or upregulated by estrogens in breast cancer cells. KiSS1 was found to be expressed in MDA-MB-231, MCF7, and T47D cell lines, but not in ZR75-1, L56Br, and MDA-MB-435 cells. KiSS1 mRNA levels decreased significantly in ERalpha-negative MDA-MB-231 cells expressing recombinant ERalpha. In contrast, tamoxifen (TAM) treatment of ERalpha-positive MCF7 and T47D cells increased KiSS1 and GPR54 levels. The clinical relevance of this negative regulation of KiSS1 and GPR54 by E(2) was then studied in postmenopausal breast cancers. KiSS1 mRNA increased with the grade of the breast tumors. ERalpha-positive invasive primary tumors expressed sevenfold lower KiSS1 levels than ERalpha-negative tumors. Among ERalpha-positive breast tumors from postmenopausal women treated with TAM, high KiSS1 combined with high GPR54 mRNA tumoral levels was unexpectedly associated with shorter relapse-free survival (RFS) relative to tumors expressing low tumoral mRNA levels of both genes. The contradictory observation of putative metastasis inhibitor role of kisspeptins and RFS to TAM treatment suggests that evaluation of KiSS1 and its receptor tumoral mRNA levels could be new interesting markers of the tumoral resistance to anti-estrogen treatment.
Study Information
pubmed
2007
10.1677/erc-07-0012