High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers

Ahlin, Cecilia; Lundgren, Claudia; Embretsen-Varro, Elin; Jirström, Karin; Blomqvist, Carl; Fjällskog, Marie-Louise

doi:10.1007/s10549-017-4294-5

Cited by 81 publications

(88 citation statements)

References 65 publications

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“…CCND1 and CCND2 belong to the D-type cyclin family, which is commonly regarded as a human cancer promoter. The elevation of CCND1 and CCND2 expression was associated with cancer metastasis [18,19,36]. The research performed by the Delmer group demonstrated that CCND2 was overexpressed in chronic B cell malignancies [37].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer

Chang¹,

Guo²,

Zhang³

et al. 2018

Cell Physiol Biochem

102

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Background/Aims: The long noncoding RNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been demonstrated to be a vital modulator in the proliferation and metastasis of ovarian cancer cells, but its potential molecular mechanism remains to be elucidated. In the current study, we aimed to uncover the biological role of lncRNA HOTAIR and its underlying regulatory mechanism in the progression and metastasis of ovarian cancer. Methods: HOTAIR expression was detected by quantitative RT-PCR (qRT-PCR) and northern blotting. The SKOV3 ovarian cancer cell line was chosen for the subsequent assays. In addition, the molecular mRNA and protein expression levels were examined by qRT-PCR and western blotting. The competitive endogenous RNA (ceRNA) mechanism was validated by bioinformatics analysis and a dual luciferase reporter gene assay. Results: HOTAIR expression was significantly higher in ovarian carcinoma tissues and cell lines than in the control counterparts. Both CCND1 and CCND2 were downstream targets of miR-206. The inhibition of HOTAIR elevated the expression of miR-206 and inhibited the expression of CCND1 and CCND2. Moreover, CCND1 and CCND2 were highly expressed in ovarian cancer tissues, and their expression was positively correlated with HOTAIR expression. Finally, the functional assays indicated that the anticancer effects of miR-206 could be rescued by the simultaneous overexpression of either CCND1 or CCND2 in ovarian cancer. Conclusion: HOTAIR enhanced CCND1 and CCND2 expression by negatively modulating miR-206 expression and stimulating the proliferation, cell cycle progression, migration and invasion of ovarian cancer cells.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer

Chang¹,

Guo²,

Zhang³

et al. 2018

Cell Physiol Biochem

102

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“…Defects in colony formation by PIP5Kα knockout were recovered by the WT, and the K88R mutant had a greater colony‐forming ability (Figure I and J). We assessed transcriptional changes in E2F1, CDK1 and CCND1 whose expression levels correlate with increased cell proliferation and are, in general, elevated in various cancers including breast cancer cells . As shown in Figure K, the mRNA expression levels of E2F1, CDK1 and CCND1 were reduced, but conversely, the mRNA levels of the tumour suppressor FOXO3 were increased in the PIP5Kα knockout SKBR3 cells compared to those in non‐targeting control cells.…”

Section: Resultsmentioning

confidence: 99%

NEDD4‐induced degradative ubiquitination of phosphatidylinositol 4‐phosphate 5‐kinase α and its implication in breast cancer cell proliferation

Tran

Seo

Min

et al. 2018

J Cellular Molecular Medi

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Phosphatidylinositol 4‐phosphate 5‐kinase (PIP5K) family members generate phosphatidylinositol 4,5‐bisphosphate (PIP2), a critical lipid regulator of diverse physiological processes. The PIP5K‐dependent PIP2 generation can also act upstream of the oncogenic phosphatidylinositol 3‐kinase (PI3K)/Akt pathway. Many studies have demonstrated various mechanisms of spatiotemporal regulation of PIP5K catalytic activity. However, there are few studies on regulation of PIP5K protein stability. Here, we examined potential regulation of PIP5Kα, a PIP5K isoform, via ubiquitin‐proteasome system, and its implication for breast cancer. Our results showed that the ubiquitin ligase NEDD4 (neural precursor cell expressed, developmentally down‐regulated gene 4) mediated ubiquitination and proteasomal degradation of PIP5Kα, consequently reducing plasma membrane PIP2 level. NEDD4 interacted with the C‐terminal region and ubiquitinated the N‐terminal lysine 88 in PIP5Kα. In addition, PIP5Kα gene disruption inhibited epidermal growth factor (EGF)‐induced Akt activation and caused significant proliferation defect in breast cancer cells. Notably, PIP5Kα K88R mutant that was resistant to NEDD4‐mediated ubiquitination and degradation showed more potentiating effects on Akt activation by EGF and cell proliferation than wild‐type PIP5Kα. Collectively, these results suggest that PIP5Kα is a novel degradative substrate of NEDD4 and that the PIP5Kα‐dependent PIP2 pool contributing to breast cancer cell proliferation through PI3K/Akt activation is negatively controlled by NEDD4.

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“…In breast cancer, there is a close relationship between ER expression and the effect on cyclin D1 expression on cell cycle activation and prognosis. 7 To test whether this is the case also in desmoid tumors, we tested the association between cyclin D1 and proliferation separately in groups defined by ERβ expression. We found no signs of modification of ERβ expression on the association between cyclin D1 and increased proliferation in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Cyclin D1 activates cyclin‐dependent kinases (Cdk) 4 and 6, which function as a complex in transition from G1 checkpoint to the S phase by phosphorylating the retinoblastoma tumor suppressor protein. ERα upregulates cyclin D1 in breast cancer and thus inhibition of ERα with endocrine agents results in cell cycle arrest . In hormone refractory breast cancer and other cancers, various proliferative pathways may induce cyclin D1 and Cdk 4/6, such as PI3K .…”

Section: Introductionmentioning

confidence: 99%

“…ERα upregulates cyclin D1 in breast cancer and thus inhibition of ERα with endocrine agents results in cell cycle arrest. 7 In hormone refractory breast cancer and other cancers, various proliferative pathways may induce cyclin D1 and Cdk 4/6, such as PI3K. 8 Highly specific Cdk inhibitors target Cdk 4 and 6 and act synergistically with hormonal therapy in breast cancer.…”

mentioning

confidence: 99%

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Estrogen receptor beta expression correlates with proliferation in desmoid tumors

Santti

Ihalainen

Rönty

et al. 2019

Journal of Surgical Oncology

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Background and objectives Estrogen receptor signaling and cyclin D1 have a major role in tumor cell proliferation in breast cancer. Desmoid tumors are rare neoplasms that may respond to endocrine treatment. The present study aimed to investigate the expression levels and the clinical relevance of estrogen receptor beta (ERβ) and cyclin D1 in desmoid tumors. Methods This study consists of 83 patients with a surgically treated desmoid tumor. ERβ and cyclin D1 expression was examined by immunohistochemistry in tissue microarrays. Cyclin A and Ki67 were studied in our previous work. Results Median ERβ expression was 10.8%. ERβ expression correlated with expression of the proliferation antigens Ki67 (rp = 0.35, P = 0.003), cyclin D1 (rp = 0.34, P = 0.004), and cyclin A (rp = 0.34, P = 0.004). ERβ immunoexpression showed a trend towards predictive impact for recurrence as a continuous variable. Further explorative analysis indicated that very high ERβ expression was related to high risk of relapse (hazard ratio [HR] 2.6; P = 0.02).Median cyclin D1 expression was 15.6%. High cyclin D1 expression was associated with high Ki67 and cyclin A expression. Cyclin D1 was not associated with time to recurrence. Conclusions ERβ and cyclin D1 immunopositivity correlated with high proliferation in desmoid tumors. High ERβ expression might be predictive for postoperative recurrence.

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High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers

Cited by 81 publications

References 65 publications

LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer

LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer

NEDD4‐induced degradative ubiquitination of phosphatidylinositol 4‐phosphate 5‐kinase α and its implication in breast cancer cell proliferation

Estrogen receptor beta expression correlates with proliferation in desmoid tumors

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