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PMID: 10487850 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Collagen receptor control of epithelial morphogenesis and cell cycle progression.

The American journal of pathology ·Vol. 155 ·No. 3 ·1999-09-00 ·Pages 927-40

Zutter MM, Santoro SA, Wu JE, Wakatsuki T, Dickeson SK, Elson EL

Abstract

To define the unique contributions of the alpha subunit cytoplasmic tails of the alpha(1)beta(1) and alpha(2)beta(1) integrin to epithelial differentiation and branching morphogenesis, a variant NMuMG cell line lacking alpha(1)beta(1) and alpha(2)beta(1) integrin expression was stably transfected with the full-length alpha(2) integrin subunit cDNA (X2C2), chimeric cDNA consisting of the extracellular and transmembrane domains of the alpha(2) subunit and the cytoplasmic domain of the alpha(1) subunit (X2C1), or alpha(2) cDNA truncated after the GFFKR sequence (X2C0). The X2C2 and X2C1 transfectants effectively adhered, spread, and formed focal adhesion complexes on type I collagen matrices. The X2C0 transfectants were less adherent to low concentrations of type I collagen, spread less well, and formed poorly defined focal adhesion complexes in comparison to the X2C2 and X2C1 transfectants. The X2C2 and X2C1 transfectants but not the X2C0 transfectants proliferated on collagen substrates. Only the X2C2 transfectants developed elongate branches and tubules in three-dimensional collagen gels and migrated on type I collagen. These findings suggest a unique role for the alpha(2) integrin cytoplasmic domain in postligand binding events and cooperative interactions with growth factors that mediate epithelial differentiation and branching morphogenesis. Either intact alpha(1) or alpha(2) integrin subunit cytoplasmic domain can promote cell cycle progression.

MeSH Terms
Animals Blotting, Western Cell Adhesion/genetics Cell Cycle/physiology Cell Differentiation/genetics Cell Division/genetics Cell Line Clone Cells/metabolism Collagen/metabolism Epithelial Cells/cytology,metabolism Female Fibronectins/metabolism Flow Cytometry Fluorescent Antibody Technique Humans Integrins/biosynthesis,genetics,physiology Mammary Glands, Animal/cytology Mice Receptors, Collagen
Chemicals
Fibronectins Integrins Receptors, Collagen Collagen
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zutter M M
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri, USA.
Santoro S A
Wu J E
Wakatsuki T
Dickeson S K
Elson E L
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65192-9
Published
1999-09-00
Pages
927-40
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1866884
Subset
IM
Grants
NCI NIH HHS · R01 CA070275 · United States
NCI NIH HHS · CA70275 · United States
NHLBI NIH HHS · HL 40506 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65192-9 PMC Full Text View journal details
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