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Gene Expression in the Third Dimension: The ECM-nucleus Connection

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Abstract

Decades ago, we and others proposed that the dynamic interplay between a cell and its surrounding environment dictates cell phenotype and tissue structure. Whereas much has been discovered about the effects of extracellular matrix molecules on cell growth and tissue-specific gene expression, the nuclear mechanisms through which these molecules promote these physiological events remain unknown. Using mammary epithelial cells as a model, the purpose of this review is to discuss how the extracellular matrix influences nuclear structure and function in a three-dimensional context to promote epithelial morphogenesis and function in the mammary gland.

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Abbreviations

ECM:

extracellular matrix

LrECM:

laminin-rich extracellular matrix

CTs:

chromosome territories

ES:

embyronic stem

MEC:

mammary epithelial cell

Col-IV:

collagen type IV

Col-I:

collagen type I

LN1:

laminin type I

LN5:

laminin type V

BM:

basement membrane

ILK:

integrin-linked kinase

PrlR:

prolactin receptor

STAT5:

signal transducer and activator of transcription 5

KASH:

Klarsicht, ANC-1, Syne Homology

SUN:

Sad1p, UNC-84

Jak2:

Just-Another-Kinase 2

BCE-1:

bovine β-casein ECM response element

NuMA:

nuclear mitotic apparatus

PML:

promyelocytic leukemia

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Acknowledgements

We thank Rana Mroue and Joni Mott for their constructive comments in the writing of this manuscript. This work was supported by grants from the U.S. Department of Energy, the Office of Biological and Environmental Research (contract no. DE-AC02-05CH1123), a Low Dose Radiation Program and a Distinguished Fellow Award from the Office of Health and Environmental Research Health Effects Division (contract no. 03-76SF00098) to MJB, the National Cancer Institute (awards R01CA064786, U54CA126552 and U54CA112970 to MJB and R01CA057621 to MJB and Zena Werb), the U.S. Department of Defense Medical and Materiel Command innovator award (contract no.W81XWH0810736 and W81XWH0510338) to MJB, and postdoctoral fellowships W81XWH0410581 to V.A.S and DAMD17-02-1-0441 to R.X., and a post-doctoral fellowship to V.A.S. from the Canadian Institutes of Health Research.

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  1. Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977R225A, Berkeley, CA, 94720, USA

    Virginia A. Spencer, Ren Xu & Mina J. Bissell

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  1. Virginia A. Spencer
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Correspondence to Virginia A. Spencer or Mina J. Bissell.

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Spencer, V.A., Xu, R. & Bissell, M.J. Gene Expression in the Third Dimension: The ECM-nucleus Connection. J Mammary Gland Biol Neoplasia 15, 65–71 (2010). https://doi.org/10.1007/s10911-010-9163-3

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