Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.
Department of Pharmaceutical Technology and Biochemistry Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland.
Int J Mol Sci. 2022 May 5;23(9):5164. doi: 10.3390/ijms23095164.
The molecular mechanisms of telomerase reverse transcriptase ( upregulation in breast cancer (BC) are complex. We compared genetic variability within and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the , , and genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of and . Only in BC patients was a correlation found between the expression of the and genes and between and . We found associations between genotypes (rs2735940 and rs10069690) and expression and telomere length. BC patients with the genotype rs2735940 have a shorter telomere length, but patients with allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the and had a longer telomere. Our results bring new insight into the regulation of , , and gene expression related to genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness.
端粒酶逆转录酶 (TERT) 的分子机制在乳腺癌 (BC) 中上调是复杂的。我们比较了 和端粒长度的基因多态性与 BC 患者的临床数据。此外，我们还评估了 BC 患者和 BC 类器官（从乳腺癌组织中获得的 3D 细胞培养物）中 、 、 和 基因的表达。我们在 BC 患者的血液和 BC 类器官中观察到 和 之间相同的相关性。只有在 BC 患者中， 和 基因之间以及 和 之间的表达才存在相关性。我们发现 基因型（rs2735940 和 rs10069690）与 表达和端粒长度之间存在关联。携带 rs2735940 基因型的 BC 患者端粒较短，但携带 rs10069690 等位基因的患者端粒较长。具有短等位基因 VNTR-MNS16A 的 BC 患者 和 基因表达较高，端粒较长。我们的研究结果为与 基因遗传多态性和端粒长度相关的 、 、 和 基因表达调控提供了新的见解。我们的研究还首次表明，BC 患者和 BC 类器官中上述基因的表达存在相似的关系。这些发现表明， 基因遗传多态性、表达和端粒长度可能是 BC 的有用生物标志物，但它们的预后价值可能因 BC 患者的临床参数和肿瘤侵袭性而异。
