Protein kinases orchestrate cell cycle regulators in differentiating BeWo choriocarcinoma cells

Kumar, M. Naveen and Babu, RL and Patil, Rajeshwari H and Kumar, KM Kiran and Hegde, Shubha M and Nagesh, Rashmi and Kavya, K and Ramesh, Govindarajan T and Sharma, S Chidananda and Srinivas, C (2019) Protein kinases orchestrate cell cycle regulators in differentiating BeWo choriocarcinoma cells. In: MOLECULAR AND CELLULAR BIOCHEMISTRY, 452 (1-2). pp. 1-15.

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Abstract

Choriocarcinoma, a trophoblastic neoplasia, occurs in women as an incidence of abnormal pregnancy. BeWo choriocarcinoma cells derived from the abnormal placentation are a suitable model system to study the factors associated with differentiation, invasion and other cellular events as an alternative to clinical samples. Many protein kinases orchestrate the complex events of cell cycle and in case of malignancy such regulators are found to be mutated. In the present study, BeWo cells treated with forskolin (Fo) and phorbol 12-myristate 13-acetate (PMA) were used to study the role of PKA (protein kinase A) and PKC (protein kinase C), respectively, on the expression pattern of differentiation-related genes, membrane markers, PKC isoforms and cell cycle regulators. The effect of Fo and PMA on the cell proliferation was assessed. Progressive induction of alkaline phosphatase level and formation of multinucleated differentiated cells were observed in the cells treated with Fo. Exposure of cells to Fo and PMA induced the mRNA transcripts of -hCG, -hCG and endoglin and down-regulates E-cadherin at mRNA and protein levels. Synergistic levels of both up- and down-regulated genes/proteins were observed when cells were treated with the combination of Fo and PMA. The mRNA levels of cyclin D1, cyclin E1, p21, Rb, p53, caspase-3 and caspase-8 decreased gradually during differentiation. Fo significantly inhibited the protein levels of PCNA, Rb, PKC- and PMA stimulated mRNA expression of PKC-epsilon and PKC-. Further, failure in the activation of essential components of the cell cycle machinery caused G2/M phase arrest in differentiating BeWo cells.

Item Type:	Journal Article
Publication:	MOLECULAR AND CELLULAR BIOCHEMISTRY
Publisher:	SPRINGER
Additional Information:	Copyright of this article belongs to SPRINGER
Keywords:	BeWo choriocarcinoma cells; Cell cycle; Differentiation; Forskolin; Phorbol esters; Protein kinases
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	26 Feb 2019 05:05
Last Modified:	26 Feb 2019 05:05
URI:	http://eprints.iisc.ac.in/id/eprint/61827

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