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Inhibitor of differentiation 1 (Id1) promotes cell survival and proliferation of prostate epithelial cells

Abstract

Id1 (inhibitor of differentiation 1) is a member of the bHLH protein family. Consistent with its role in promoting proliferation and inhibiting differentiation, Id1 expression is low or negligible in normal prostate epithelial cells but is high in prostate cancer. Ectopic expression of Id1 in normal prostate epithelial cells could therefore provide a model for understanding early events involved in initiation of prostate cancer. Over-expression of Id1 immortalized but did not transform ventral prostate epithelial cells (Id1-RPE). Immortalization was associated with decreased Cdkn2a, Cdkn1a, androgen receptor and increased Tert expression. Gene expression profiling over successive doublings was used to identify transcriptomic changes involved during immortalization (Tieg, Jun, alpha actin, Klf10, Id2) and in maintaining the immortalized phenotype (Igfbp3, Igfbp5, Mmp2, Tgfb3). Network analysis indicated that Id1 promotes cancer/tumor morphology, cell cycle and epithelial to mesenchymal transition by influencing AP1, tnf, tgfβ, PdgfBB and estradiol pathways. During immortalization, the expression of majority of differentially expressed genes reduced over progressive doublings suggesting a decline in transcriptional regulatory mechanisms. The associated molecular/gene expression profile of Id1-RPE cells provides an opportunity to understand the molecular pathways associated with prostate epithelial cell survival and proliferation.

Abbreviations

bHLH:

basic helix loop helix

CDKI:

cyclin dependent kinase inhibitor

EMT:

epithelial - mesenchymal transition

HGF:

hepatocyte growth factor

Id:

inhibitor of differentiation

KGF:

keratinocyte growth factor

MAPK:

mitogen activated protein kinase

NHUC:

normal human urothelial cells

PrEC:

prostate epithelial cells (human)

R1881:

methyltrienolone (non-aromatizable synthetic androgen analogue)

RPE:

rat prostate epithelial

TERT:

telomerase reverse transcriptase

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Correspondence to Jaideep Chaudhary.

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Schmidt, M., Asirvatham, A.J. & Chaudhary, J. Inhibitor of differentiation 1 (Id1) promotes cell survival and proliferation of prostate epithelial cells. Cell Mol Biol Lett 15, 272–295 (2010). https://doi.org/10.2478/s11658-010-0007-3

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Key words

  • Id1
  • Prostate
  • epithelial cells
  • Immortalization
  • Cancer