Talk give at 34<sup>th</sup> Annual
Convention of Indian Association for Cancer Research (<b>IACR2015</b>), 19<sup>th </sup>–
21<sup>st</sup> February 2015 Jaipur. <div><b><br></b><div><b>Abstract: </b>It is now well established that cells in a tumor are
heterogeneous. Such heterogeneity originates for various reasons, including accumulation
of random mutations. It is commonly assumed that a population of genetically
identical, clonally-derived, cells will be homogenous and all the cells in that
population would behave similarly. However, that is not true. Like many other
cellular processes, expression of a gene is stochastic. Such stochasticity
leads to non-genetic cellular heterogeneity in gene expression. Heterogeneity
in gene expression often leads to different phenotypic states within a
population of cells. Design of the transcriptional circuit affects the
heterogeneity. A positive feedback, in a transcriptional circuit, amplifies
noise in gene expression and often triggers emergence of two subpopulations.
Here, in this work we show that transcription of an oncofetal protein human
Cripto-1 (CR-1) is regulated through an autoregulatory positive feedback. We
characterize this feedback using biochemical tools. We further show that
induction of this circuit leads to
spontaneous emergence of two sub-populations, having higher and lower expression
of CR-1. Such heterogeneity in CR-1 expression is observed in clinical samples
and in multiple cancer cell lines. We use both experimental and mathematical
simulation to understand the phenomenon. We have observed that MDR-1, a drug
resistance gene, is also co-induced in the subpopulation having higher
expression of CR-1. Our work emphasizes involvement of CR-1 in the phenotypic diversification of
cancer cells and spontaneous emergence of probable drug resistant
subpopulation.</div><p> <br></p></div
