Expression of SnoRNA U50A Is Associated with Better Prognosis and Prolonged Mitosis in Breast Cancer

Small nucleolar RNAs (snoRNAs) are small noncoding RNAs generally recognized as housekeeping genes. Genomic analysis has shown that snoRNA U50A (U50A) is a candidate tumor suppressor gene deleted in less than 10% of breast cancer patients. To date, the pathological roles of U50A in cancer, including its clinical significance and its regulatory impact at the molecular level, are not well-defined. Here, we quantified the copy number of U50A in human breast cancer tissues. Our results showed that the U50A expression level is correlated with better prognosis in breast cancer patients. Utilizing RNA-sequencing for transcriptomic analysis, we revealed that U50A downregulates mitosis-related genes leading to arrested cancer cell mitosis and suppressed colony-forming ability. Moreover, in support of the impacts of U50A in prolonging mitosis and inhibiting clonogenic activity, breast cancer tissues with higher U50A expression exhibit accumulated mitotic tumor cells. In conclusion, based on the evidence from U50A-downregulated mitosis-related genes, prolonged mitosis, repressed colony-forming ability, and clinical analyses, we demonstrated molecular insights into the pathological impact of snoRNA U50A in human breast cancer.

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Antiestrogen-resistant human breast cancer cells require activated Protein Kinase B/Akt for growth

Endocrine Related Cancer ◽

10.1677/erc.1.00946 ◽

2005 ◽

Vol 12 (3) ◽

pp. 599-614 ◽

Cited By ~ 57

Author(s):

T Frogne ◽

J S Jepsen ◽

S S Larsen ◽

C K Fog ◽

B L Brockdorff ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Cell Lines ◽

Human Breast Cancer ◽

Neutralizing Antibodies ◽

Breast Cancer Cells ◽

Resistant Cell ◽

Breast Cancer Patients ◽

Human Breast ◽

Mcf 7

Development of acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. The IGF system plays a profound role in many cancer types, including breast cancer. Thus, overexpression and/or constitutive activation of the IGF-I receptor (IGF-IR) or different components of the IGF-IR signaling pathway have been reported to render breast cancer cells less estrogen dependent and capable of sustaining cell proliferation in the presence of antiestrogens. In this study, growth of the antiestrogen-sensitive human breast cancer cell line MCF-7 was inhibited by treatment with IGF-IR-neutralizing antibodies. In contrast, IGF-IR-neutralizing antibodies had no effect on growth of two different antiestrogen-resistant MCF-7 sublines. A panel of antiestrogen-resistant cell lines was investigated for expression of IGF-IR and either undetectable or severely reduced IGF-IR levels were observed. No increase in insulin receptor substrate 1 (IRS-1) or total PKB/Akt (Akt) was detected in the resistant cell lines. However, a significant increase in phosphorylated Akt (pAkt) was found in four of six antiestrogen-resistant cell lines. Overexpression of pAkt was associated with increased Akt kinase activity in both a tamoxifen- and an ICI 182,780-resistant cell line. Inhibition of Akt phosphorylation by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin or the Akt inhibitor SH-6 (structurally modified phosphatidyl inositol ether liquid analog PIA 6) resulted in a more pronounced growth inhibitory effect on the antiestrogen-resistant cells compared with the parental cells, suggesting that signaling via Akt is required for antiestrogen-resistant cell growth in at least a subset of our antiestrogen-resistant cell lines. PTEN expression and activity was not decreased in cell lines overexpressing pAkt. Our data demonstrate that Akt is a target for treatment of antiestrogen-resistant breast cancer cell lines and we suggest that antiestrogen-resistant breast cancer patients may benefit from treatment targeted to inhibit Akt signaling.

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Selective Cox-2 inhibition attenuates the perioperative increase of the tumour enhancing pro-angiogenic cytokine Vegf in human breast cancer patients

Journal of Surgical Research ◽

10.1016/j.jss.2003.08.140 ◽

2003 ◽

Vol 114 (2) ◽

pp. 243 ◽

Cited By ~ 2

Author(s):

G.T. O’Donoghue ◽

G. Roche-Nagle ◽

E.M. Connolly ◽

J. Harmey ◽

D.J. Bouchier-Hayes

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Human Breast Cancer ◽

Breast Cancer Patients ◽

Human Breast ◽

Cox 2

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The Hedgehog signalling pathway mediates drug response of MCF-7 mammosphere cells in breast cancer patients

Clinical Science ◽

10.1042/cs20140592 ◽

2015 ◽

Vol 129 (9) ◽

pp. 809-822 ◽

Cited By ~ 24

Author(s):

Miao He ◽

Yingzi Fu ◽

Yuanyuan Yan ◽

Qinghuan Xiao ◽

Huizhe Wu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Human Breast Cancer ◽

Drug Response ◽

Breast Cancer Patients ◽

Human Breast ◽

Hedgehog Signalling ◽

Hedgehog Signalling Pathway ◽

Xenograft Mice ◽

Mcf 7

Our study showed that Hh signalling activation contributed to BCSC-mediated chemoresistance in cultured breast cancer MCF-7 MS cells, in xenograft mice and in human breast cancer patients.

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S295 THE EFFECT OF COMT-GENOTYPE ON EXPERIMENTAL AND CLINICAL POSTOPERATIVE PAIN IN HUMAN BREAST CANCER PATIENTS

European Journal of Pain Supplements ◽

10.1016/s1754-3207(11)70860-4 ◽

2011 ◽

Vol 5 (S1) ◽

pp. 249-249

Author(s):

O. Kambur ◽

M. Kaunisto ◽

D.J. Liu ◽

A. Palotie ◽

S.M. Leal ◽

...

Keyword(s):

Breast Cancer ◽

Postoperative Pain ◽

Cancer Patients ◽

Human Breast Cancer ◽

Breast Cancer Patients ◽

Human Breast ◽

Comt Genotype

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TMEM71 expression associates with survival in triple negative breast cancer.

10.31219/osf.io/djgqs ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Human Breast Cancer ◽

Triple Negative ◽

Transmembrane Protein ◽

Breast Cancer Patients ◽

Human Breast ◽

Primary Tumors ◽

Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of transmembrane protein 71, encoded by TMEM71 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, TMEM71 expression was correlated with overall survival in patients with human breast cancer. TMEM71 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

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Increased Soluble CrkL in Serum of Breast Cancer Patients Is Associated with Advanced Disease

Cancers ◽

10.3390/cancers11070961 ◽

2019 ◽

Vol 11 (7) ◽

pp. 961 ◽

Cited By ~ 1

Author(s):

Srimeenakshi Srinivasan ◽

Biana Godin

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Cell Lines ◽

Breast Cancer Cell ◽

Human Breast Cancer ◽

Advanced Disease ◽

Human Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Breast Cancer Patients ◽

Human Breast

Over-expression of Crk-like protein (CrkL), an intracellular adaptor protein, in breast cancer biopsies has been linked to poor prognosis. CrkL can be secreted from cancer cells binding to β1 integrin on the cell membrane. In this study, we evaluated, for the first time, the levels of soluble CrkL in serum of breast cancer patients. Expression of CrkL and secreted fractions from human breast cancer cell lines and clinical patient samples were assessed by immunohistochemistry and Enzyme Linked Immuno-Sorbent Assay (ELISA). CrkL levels in tissues and sera of patients with different disease stages were compared and statistically analyzed by Chi-square test and Student’s t-test. Culture media from human breast cancer cell lines SUM159, MDA-MB231, and MCF7 showed over a 21-, 15-, and 11-fold higher concentration of soluble CrkL as compared to normal breast epithelium cell line MCF10A. Expression of CrkL was elevated in 85% of breast tumor tissue sections. Serum levels of CrkL were significantly higher in breast cancer patients than in healthy donors. All patients with metastatic disease had significantly elevated concentration of soluble CrkL in the serum with on average three-fold increase from the baseline. The data suggest that soluble fraction of CrkL can be further evaluated as a serum biomarker for advanced disease in breast cancer patients.

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