Interaction of pRb and β-Catenin in Cancer and Normal Human Prostate Tissue

Q4 Biochemistry, Genetics and Molecular Biology Cell and Tissue Biology Pub Date : 2024-06-03 DOI:10.1134/s1990519x24700238

V. M. Ryabov, N. I. Tyapkin, A. P. Rodimtsev, O. G. Lyublinskaya, I. V. Guzhova, B. V. Popov

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Abstract

Prostate cancer (PCa) is one of the most common oncological diseases, which passes through two stages in its development: localized PCa and castration-resistant PCa (CR-PCa). The first stage—localized prostate cancer—can proceed indefinitely in a dormant form that does not require active medical intervention, or suddenly turn into an aggressive metastatic form (CR-PCa), ending in rapid death. The pathogenesis of the transition of the dormant form of PCa to the metastatic form remains not fully understood. The signaling pathways of tumor suppressor pRb and proto-oncogene β-catenin are probably the most involved in the pathogenesis of prostate cancer, but the role of their interaction has not been studied. The publication on the pathogenesis of tumors in other tissues suggests that pRb may lose some properties of a tumor suppressor at the initial stage of PCa development due to its interaction with β-catenin that enables tumor cells to gain competitive advantages for reproduction. In this work, we showed that the genes RB and β-catenin (CTNNB1) are expressed in tumor and normal prostate tissue. Unlike β-catenin, pRb is not detected by immunoblotting in tumor and normal prostate tissue, but is easily detected in this way in extracts of control T98G cells. Co-immunoprecipitation with antibodies to pRb from extracts of tumor and normal prostate tissue makes it possible to detect this protein and β-catenin by subsequent immunoblotting, which indicates the physical interaction of these proteins in prostate tissue. On the other hand, immunoprecipitation of β-catenin with antibodies to its C-terminal fragment does not make it possible to detect this protein in prostate extracts by subsequent immunoblotting using the same antibodies. In contrast to prostate tissue, β-catenin was readily detected by immunoprecipitation coupled with immunoblotting in extracts of control T98G cells. The obtained data suggest that pRb and β-catenin physically interact with each other in cells of different tissue specificity. In T98G cells, this interaction probably occurs through the C-terminal fragment of β-catenin, but in prostate cells it occurs in a different way, since the C fragment of β-catenin is shielded from such interaction, possibly due to its physical association with pRb.

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癌症和正常人前列腺组织中 pRb 和 β-Catenin 的相互作用

摘要前列腺癌（PCa）是最常见的肿瘤疾病之一，在其发展过程中会经历两个阶段：局部性前列腺癌和阉割抗性前列腺癌（CR-PCa）。第一阶段--局部性前列腺癌--可能以休眠状态无限期发展，不需要积极的医疗干预，也可能突然转变为侵袭性转移性前列腺癌（CR-PCa），最终导致患者迅速死亡。休眠型 PCa 向转移型 PCa 过渡的发病机制仍未完全明了。肿瘤抑制因子 pRb 和原癌基因 β-catenin 的信号通路可能是前列腺癌发病机制中参与度最高的，但它们之间的相互作用尚未得到研究。有关其他组织肿瘤发病机理的研究结果表明，pRb 在 PCa 发病初期可能会因与 β-catenin 的相互作用而丧失肿瘤抑制因子的某些特性，从而使肿瘤细胞获得繁殖竞争优势。在这项研究中，我们发现 RB 和 β-catenin（CTNNB1）基因在肿瘤和正常前列腺组织中均有表达。与β-catenin不同，pRb在肿瘤和正常前列腺组织中无法通过免疫印迹检测到，但在对照组T98G细胞的提取物中很容易被检测到。在肿瘤和正常前列腺组织的提取物中与 pRb 抗体共免疫沉淀，可以在随后的免疫印迹中检测到该蛋白和 β-catenin，这表明这些蛋白在前列腺组织中存在物理相互作用。另一方面，用 C 端片段抗体免疫沉淀 β-catenin，并不能在随后的免疫印迹中检测到前列腺提取物中的该蛋白。与前列腺组织不同的是，在对照组 T98G 细胞的提取物中，通过免疫沉淀和免疫印迹法很容易检测到 β-catenin。所获得的数据表明，pRb 和 β-catenin 在不同组织特异性的细胞中会发生物理相互作用。在 T98G 细胞中，这种相互作用可能是通过 β-catenin 的 C 端片段发生的，但在前列腺细胞中，这种相互作用以不同的方式发生，因为 β-catenin 的 C 片段被屏蔽在这种相互作用之外，这可能是由于它与 pRb 的物理关联。

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来源期刊

Cell and Tissue Biology Biochemistry, Genetics and Molecular Biology-Cell Biology

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0.80

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0.00%

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期刊介绍： The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.