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

被引：0

作者：

Ryabov V.M. ^{[1
]}

Tyapkin N.I. ^{[2
]}

Rodimtsev A.P. ^{[1
]}

Lyublinskaya O.G. ^{[1
]}

Guzhova I.V. ^{[1
]}

Popov B.V. ^{[1
]}

机构：

[1] Institute of Cytology, Russian Academy of Sciences, St. Petersburg

[2] Roman Leningrad Regional Clinical Oncology Dispensary, Ministry of Health of the Russian Federation, Kuzmolovo

来源：

Cell and Tissue Biology | 2024年 / 18卷 / 3期

基金：

俄罗斯科学基金会;

关键词：

interaction of pRb and β‑catenin in PCa; localized prostate cancer (PCa); signal pathways pRb and β-catenin;

D O I：

10.1134/S1990519X24700238

中图分类号：

学科分类号：

摘要：

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. © Pleiades Publishing, Ltd. 2024. ISSN 1990-519X, Cell and Tissue Biology, 2024, Vol. 18, No. 3, pp. 296–306. Pleiades Publishing, Ltd., 2024. Russian Text The Author(s), 2024, published in Tsitologiya, 2024, Vol. 66, No. 1, pp. 64–76.

引用

页码：296 / 306

页数：10

共 39 条

[1]

Balk S.P., Knudsen K.E., AR, the cell cycle, and prostate cancer, Nucl. Recept. Signal, 6, (2008)

[2]

Comprehensive molecular characterization of human colon and rectal cancer, Nature, 487, (2012)

[3]

Chau B.N., Borges H.L., Chen T.T., Masselli A., Hunton I.C., Wang J.Y., Signal-dependent protection from apoptosis in mice expressing caspase-resistant Rb, Nat. Cell Biol, 4, (2002)

[4]

Ciavarra G., Zacksenhaus E., Direct and indirect effects of the pRb tumor suppressor on autophagy, Autophagy, 7, (2011)

[5]

Cunha G.R., Role of mesenchymal-epithelial interactions in normal and abnormal development of the mammary gland and prostate, Cancer, 74, (1994)

[6]

Derenzini M., Donati G., Mazzini G., Montanaro L., Vici M., Ceccarelli C., Santini D., Taffurelli M., Trere D., Loss of retinoblastoma tumor suppressor protein makes human breast cancer cells more sensitive to antimetabolite exposure, Clin. Cancer Res, 14, (2008)

[7]

Dick F.A., Goodrich D.W., Sage J., Dyson N.J., Non-canonical functions of the RB protein in cancer, Nat. Rev. Cancer, 18, (2018)

[8]

Dyson N., The regulation of E2F by pRB-family proteins, Genes Dev, 12, (1998)

[9]

Friend S.H., Bernards R., Rogelj S., Weinberg R.A., Rapaport J.M., Albert D.M., Dryja T.P., A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma, Nature, 323, (1986)

[10]

Han J., Soletti R.C., Sadarangani A., Sridevi P., Ramirez M.E., Eckmann L., Borges H.L., Wang J.Y., Nuclear expression of β-catenin promotes RB stability and resistance to TNF-induced apoptosis in colon cancer cells, Mol. Cancer Res, 11, (2013)

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