Pttg1 Promotes Growth of Breast Cancer through P27 Nuclear Exclusion

Abstract

Background/Aims: A role of Pituitary Tumor Transforming Gene 1 (Pttg1) in the carcinogenesis has been shown in some cancers, but not in BC (BC). Methods: We compared the levels of Pttg1 in the resected BC tissue with the adjacent normal breast tissue from the same patient. We modified Pttg1 levels in a BC cell line, MCF7, by either a Pttg1 transgene, or a Pttg1 shRNA. The cell growth was measured in an MTT assay. The cell apoptosis was measured by apoptosis assay. The nuclear protein of cell-cycle-related genes was examined in Pttg1-modifed BC cells. Co-immunoprecipitation was performed to examine the association of Pttg1 and p27. Results: We detected significantly higher levels of Pttg1 in the resected BC tissue, compared to the adjacent normal breast tissue from the same patient. Overexpression or depletion of Pttg1 in MCF7 significantly increased or inhibited cell growth, respectively. Changes in Pttg1 levels, however, did not alter cell apoptosis, suggesting that Pttg1 increases cell growth through augmented cell proliferation, rather than decreased cell apoptosis. Among all examined cell-cycle-related proteins in Pttg1-modifed BC cells, only nuclear p27 levels were significantly affected. Further, co-immunoprecipitation showed that Pttg1 directly associated with p27. Conclusion: Pttg1 may increase BC cell growth through nuclear exclusion of p27, which highlights a novel molecular regulatory machinery in tumorigenesis of BC.

Significant prognostic values of differentially expressed-aberrantly methylated hub genes in breast cancer

“…PTTG1 is a regulator in chromosomal segregation. It can promote the proliferation of breast cancer cell through binding to P27 directly to induce nuclear exclusion of P27 16. MCM4 gene encodes a kind of minichromosomal maintenance proteins.…”

High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer

“…Pituitary tumor-transforming 3, pseudogene (PTTG3P), is a processed pseudogene that shows high homology to its family members, pituitary tumor-transforming 1 (PTTG1) and -2 (PTTG2) 8 . Numerous investigations have shown that PTTG1 and -2 serve as two key oncogenes in a variety of human cancers, including breast cancer,9, 10 lung cancer, 11 pituitary adenoma, 12 and esophageal squamous cell cancer 13 . However, there are only a few reports regarding the expression and roles of PTTG3P in cancer.…”

microRNA-Dependent Modulation of Genes Contributes to ESR1's Effect on ERα Positive Breast Cancer

“…Most of these hub genes were reported as critical players in regulating occurrence and development of breast cancer. For example, Zhang et al found that nuclear AURKA acquired kinase-independent transactivating function to enhance breast cancer stem cell phenotype (32); PTTG1 promoted growth, endocrine therapy resistance of breast cancer (33)(34)(35); UBE2C post-transcriptionally upregulated by miR-196a enhanced proliferation of breast cancer cell (36). Then, we performed survival analysis for the 51 hub genes.…”