TGF\beta1 induces multiple independent signals to regulate human trophoblastic differentiation: mechanistic insights

Rama, S and Suresh, Y and Rao, AJ (2003) TGF\beta1 induces multiple independent signals to regulate human trophoblastic differentiation: mechanistic insights. In: Molecular and Cellular Endocrinology, 206 (1-2). pp. 122-136.

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Abstract

Transforming growth factor-beta 1 (TGF beta1) plays a crucial role in controlling trophoblast growth and invasion. Loss of this key regulatory function provides the pathophysiological basis for several tumors, which are characterized by uncontrolled telomerase activity. We have shown earlier that telomerase activity is negatively regulated during terminal differentiation of human trophoblasts, and that TGF beta1 may be an important factor governing the transcription of human telomerase reverse transcriptase (hTERT) (the catalytic subunit of the telomerase complex) during this process. In the present study, we extend these observations to identify possible functional effectors of TGF beta1-induced loss in telomerase activity during human trophoblastic differentiation. We show that this regulation may involve the suppression of c-Myc and an increased production of Mad1. We also observed a simultaneous increase in the expression of cyclin-dependent-kinase inhibitors, p21, p27, p15 and p16, associated with a loss in expression of Cyclin-A2 and Cyclin-E. Thus, TGF beta1 may induce multiple independent signals to check the proliferative potential of human trophoblastic cells and allow their functional differentiation.

Item Type:	Journal Article
Publication:	Molecular and Cellular Endocrinology
Publisher:	Elsevier Science
Additional Information:	Copyright of this article belongs to Elsevier Science.
Keywords:	TGF beta 1;placenta;trophoblast;proliferation; differentiation;telomerase.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Biological Sciences > Biochemistry
Date Deposited:	03 Nov 2009 10:40
Last Modified:	19 Sep 2010 04:56
URI:	http://eprints.iisc.ac.in/id/eprint/17418

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