Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors

Malinen, Marjo; Jääskeläinen, Tiina; Pelkonen, Mikko; Heikkinen, Sami; Vaïsänen, Sami; Kosma, Veli‐Matti; Nieminen, Kaisa; Mannermaa, Arto; Palvimo, Jorma J.

doi:10.1016/j.mce.2012.10.028

Cited by 43 publications

(38 citation statements)

References 44 publications

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“…CDK1 is a member of the Ser/Thr protein kinase family, and its product is a catalytic subunit of M-phase promoting factor, essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. The oncogenic character of Ser/Thr protein kinases like B-Raf and PIM1 was shown [12–14]. It was demonstrated that CDK1 is suifficient to drive the cell cycle in mammalian cells [31] which indicates the leading role of this kinase in cell cycle regulation.…”

Section: Discussionmentioning

confidence: 99%

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Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

et al. 2016

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In this study, we analyzed the expression profile of four genes (CCNA2, CCNB1, CCNB2, and CDK1) in laryngeal squamous cell carcinoma (LSCC) cell lines and tumor samples. With the application of microarray platform, we have shown the overexpression of these genes in all analyzed LSCC samples in comparison to non-cancer controls from head and neck region. We have selected CDK1 for further analysis, due to its leading role in cell cycle regulation. It is a member of the Ser/Thr protein kinase family of proven oncogenic properties. The results obtained for CDK1 were further confirmed with the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) technique, Western blot, and immunohistochemistry (IHC). The observed upregulation of CDK1 in laryngeal squamous cell carcinoma has encouraged us to analyze for genetic mechanisms that can be responsible this phenomenon. Therefore, with the application of array-CGH, sequencing analysis and two methods for epigenetic regulation analysis (DNA methylation and miRNA expression), we tried to identify such potential mechanisms. Our attempts to identify the molecular mechanisms responsible for observed changes failed as we did not observe significant alterations neither in the DNA sequence nor in the gene copy number that could underline CDK1 upregulation. Similarly, the pyrosequencing and miRNA expression analyses did not reveal any differences in methylation level and miRNA expression, respectively; thus, these mechanisms probably do not contribute to elevation of CDK1 expression in LSCC. However, our results suggest that alteration of CDK1 expression on both mRNA and protein level probably appears on the very early step of carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-016-4991-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…This gene is a member of the Ser/Thr protein kinases family. The oncogenic potential of these enzymes was demonstrated [12–14]. The CDK1 protein is a catalytic subunit of M-phase promoting factor essential for the G1/S and G2/M transition in eukaryotic cell cycle.…”

Section: Introductionmentioning

confidence: 99%

Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

et al. 2016

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“…Previous studies have suggested that PIM-1 is important for carcinogenesis and metastasis in numerous types of human cancer (6)(7)(8)(9)(10)(11)(12). The present study selected 4 pairs of ACC tissue and corresponding normal tissues and revealed that PIM-1 was overexpressed in ACC.…”

Section: Discussionmentioning

confidence: 71%

“…PIM-1, Pim-1 proto-oncogene, serine/threonine kinase (PIM-1) is upregulated in a number of cancer subtypes and the overexpression of PIM-1 is thought to be involved in cancer-specific apoptosis signaling pathways (6)(7)(8)(9)(10)(11)(12). Apoptosis is modulated by complex pathways that involve a series of apoptosis-associated proteins.…”

Section: Introductionmentioning

confidence: 99%

Expression of PIM‑1 in salivary gland adenoid cystic carcinoma: Association with tumor progression and patients' prognosis

Zhu

Hou

et al. 2017

Oncol Lett

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Abstract. Pim-1 proto-oncogene, serine/threonine kinase (PIM-1) phosphorylates a series of substrates to exert its oncogenic function in numerous malignancies. The present study investigated the clinical significance of the PIM-1 protein, apoptosis status and apoptosis-associated proteins, including forkhead box O3a (FOXO3a), B cell lymphoma-2 (BCL-2) and BCL-2-associted agonist of cell death (BAD), were investigated in salivary gland adenoid cystic carcinoma (ACC) tissues. PIM-1 expression levels in 4 pairs of ACC tissues and corresponding normal salivary gland tissues were determined by western blot analysis. PIM-1, FOXO3a, BAD and BCL-2 expression levels in 60 ACC tissues were evaluated by immunohistochemistry (IHC). A terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay was performed to detect the apoptosis status of ACC tissues. PIM-1 was revealed to be highly expressed in ACC tissues compared with adjacent normal tissues. IHC staining results demonstrated high expression ratios of PIM-1, FOXO3a, BCL-2 and BAD [33.33% (20/60), 51.67% (31/60), 51.67% (31/60) and 55% (33/60)], respectively, and significant correlations between the expression of PIM-1 and FOXO3a and BCL-2 (P<0.05). Apoptotic rates were significantly associated with PIM-1, FOXO3a, BCL-2 and BAD expression levels (P<0.05). PIM-1 expression levels were significantly associated with tumor size, lymph node involvement, nerve invasion, distant metastasis and weakly associated with tumor node metastasis stage. Kaplan-Meier survival curves revealed that PIM-1 expression level was significantly associated with disease-free survival of patients with ACC (P=0.009). Cox regression multivariate analysis results revealed that histotype, distant metastasis and apoptotic rate were independent prognosis factors for ACC. Assessment of PIM-1 may be useful in investigating the malignant behaviors of ACC and predicting the outcome of patients with ACC. IntroductionSalivary gland adenoid cystic carcinoma (ACC) accounts for ~10% of cases of epithelial salivary tumors and has a low 5-year survival rate (<20% in patients with highly metastatic tumors) (1,2). The development of ACC involves the interaction of oncogenes and tumor suppressor genes, similar to most other types of tumor (3). However, the precise mechanisms underlying ACC carcinogenesis remain to be elucidated (4,5).PIM kinases are oncogenic and are known to phosphorylate numerous substrates to exert their functions and have important roles in numerous malignancies. PIM-1, Pim-1 proto-oncogene, serine/threonine kinase (PIM-1) is upregulated in a number of cancer subtypes and the overexpression of PIM-1 is thought to be involved in cancer-specific apoptosis signaling pathways (6-12). Apoptosis is modulated by complex pathways that involve a series of apoptosis-associated proteins. As a substrate of PIM-1 kinase, Forkhead box O3a (FOXO3a) is a proapototic transcription factor and regulates the expression of numerous apoptosis-associated genes to induce apoptosis (13). It has previously ...

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“…Expression level of Pim-1 has also been shown to be predictive of poor prognosis in esophageal carcinoma [82] and gastric cancer [83]. The presence of Pim-1 in invasive breast tumors was found to be indicative of a higher tumor grade [84]. Significantly, Pim kinases are abnormally expressed in malignant lesions, but not in the normal tissues [41,[85][86][87].…”

Section: Anticancer Target Rationalementioning

confidence: 99%

Targeting Pim Kinases for Cancer Treatment: Opportunities and Challenges

Kumarasiri

Adams

et al. 2015

Future Med. Chem.

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Pim oncogenes are highly expressed in many types of hematological and solid cancers. Pim kinases regulate the network of signaling pathways that are critical for tumorigenesis and development, making Pim kinases the attractive drug targets. Currently, two approaches have been employed in designing Pim kinase inhibitors: ATP-mimetics and non-ATP mimetics; but all target the ATP-binding pocket and are ATP-competitive. In this review, we summarize the current progress in understanding the Pim-related structure and biology, and provide insights into the binding modes of some prototypical Pim-1 inhibitors. The challenges as well as opportunities are highlighted for development of Pim kinase inhibitors as potential anticancer agents.

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Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors

Cited by 43 publications

References 44 publications

Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

Expression of PIM‑1 in salivary gland adenoid cystic carcinoma: Association with tumor progression and patients' prognosis

Targeting Pim Kinases for Cancer Treatment: Opportunities and Challenges

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