A Mechanistic Study of the Estrogenic Regulation of Casein Kinase 2 alpha (CK2α) in Breast Cancer
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
A Mechanistic Study of the Estrogenic Regulation of Casein Kinase 2 alpha (CK2α) in Breast Cancer
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| Creator |
Das, Nilanjana
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| Subject |
Cancer Biology and Inflammatory Disorder Division
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| Description |
Casein kinase 2 alpha (CK2α) is a ubiquitously expressed and highly conserved
serine/threonine kinase. Protein kinase CK2α is frequently upregulated in different cancers.
Alteration of CK2α expression and its activity is sufficient to induce dramatic changes in cell
fate. Though the expression level of this vital kinase is strictly maintained under normal
cellular condition yet its deregulation has frequently been observed in colorectal, prostate and
lung cancer. It has been established that CK2α induces oncogenesis through modulation of
both AKT and PML. CK2α has been found to be overexpressed in breast cancer. In contrary,
statistical reports have shown low level of PML. However, the cause and consequences of its
overexpression are not fully understood. On the other hand, a majority of breast cancer cases
are estrogen receptor alpha (ERα) mediated where ER acting as a transcription factor plays a
key role. In recent years, it has been established that PML, a tumour suppressor is degraded
upon CK2 mediated phosphorylation. These prompted us to investigate the relationship that
the two important molecules (ERα and CK2α) share in breast cancer cells. In the current
study, we found CK2α and activated AKT positively correlate with ERα, whereas PML follows
an inverse correlation in human breast cancer tissues. Modulation of ERα signaling leads to
recruitment of activated ERα on the ERE sites of CK2α promoter, resulting in CK2α
transactivation. Furthermore, the DMBA induced tumours in rat showed elevated level of
active CK2α. Consequently it mediates enhancement of AKT activity and PML degradation,
resulting in increased cellular proliferation, migration and metastasis. Syngeneic ERα
overexpressing stable mouse 4T1 cells produce larger primary tumours and metastatic lung
nodules in mice, corroborating our in vitro findings. Hence, our study provides a novel route
of ERα dependent CK2α mediated oncogenesis that causes upregulation and consequent
AKT activation along with degradation of tumour suppressor PML.
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| Date |
2016
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2775/1/9_Thesis_Nilanjana_June_16_2016.pdf
Das, Nilanjana (2016) A Mechanistic Study of the Estrogenic Regulation of Casein Kinase 2 alpha (CK2α) in Breast Cancer. PhD thesis, University of Calcutta. |
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| Relation |
http://www.eprints.iicb.res.in/2775/
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