Mantsou Aglaia, Pitou Maria, Papachristou Eleni, Papi Rigini M, Lamprou Paraskevas, Choli-Papadopoulou Theodora
Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
Bone Rep. 2021 Sep 6;15:101125. doi: 10.1016/j.bonr.2021.101125. eCollection 2021 Dec.
Zinc Finger Protein 217 (ZNF217), a transcription factor and oncogene product, has been found to dysregulate Bone Morphogenetic Protein (BMP) signaling and induce invasion in breast tumors. In this study, the effect of BMP-2 or an active BMP-2 peptide, AISMLYLDEN, on the expression of , and CDK-inhibitor p21 gene, , was investigated in MCF-7 breast cancer cells. In parallel, the entire protein (BMP-2) as well as the aforementioned peptide were investigated in hDPSCs during osteogenic differentiation. The treatment of MCF-7 cancer cells with different concentrations of peptide AISMLYLDEN showed that the addition of 22.6 ng/ml was more effective in comparison to the other used concentrations. In particular, 48 h after treatment, and mRNA levels were substantially increased in contrast to mRNA levels which were decreased. These results are strongly supported by BrdU assay that clearly indicated inhibition of cancer cell proliferation. Taken together, these results open ways for a concurrent use, at appropriate concentrations, of the peptide AISMLYLDEN during conventional therapeutic treatment in breast tumors with a metastatic tendency to the bones. Regarding the effect of the entire protein as well as its peptide on hDPSCs differentiation into osteocytes, the mRNA levels of osteocalcin, an osteogenic marker, showed that the peptide enhanced osteogenesis at a higher degree in comparison to the entire BMP-2 without however altering , and expression levels, which remained as expected of non-cancer cells.
锌指蛋白217（ZNF217）是一种转录因子和癌基因产物，已被发现可失调骨形态发生蛋白（BMP）信号并诱导乳腺肿瘤侵袭。在本研究中，研究了BMP - 2或活性BMP - 2肽AISMLYLDEN对MCF - 7乳腺癌细胞中、和细胞周期蛋白依赖性激酶抑制剂p21基因表达的影响。同时，在人牙髓干细胞（hDPSCs）成骨分化过程中研究了完整蛋白（BMP - 2）以及上述肽。用不同浓度的肽AISMLYLDEN处理MCF - 7癌细胞表明，与其他使用的浓度相比，添加22.6 ng/ml更有效。特别是，处理48小时后，和mRNA水平显著增加，而mRNA水平则下降。BrdU检测有力地支持了这些结果，该检测清楚地表明癌细胞增殖受到抑制。综上所述，这些结果为在具有骨转移倾向的乳腺肿瘤的传统治疗过程中以适当浓度同时使用肽AISMLYLDEN开辟了道路。关于完整蛋白及其肽对hDPSCs向骨细胞分化的影响，成骨标志物骨钙素的mRNA水平表明，与完整的BMP - 2相比，该肽在更高程度上增强了成骨作用，然而并没有改变、和的表达水平，这些水平仍保持非癌细胞的预期水平。
