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PMID: 11549591 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Mammary epithelial cell-cycle progression via the alpha(2)beta(1) integrin: unique and synergistic roles of the alpha(2) cytoplasmic domain.

The American journal of pathology ·Vol. 159 ·No. 3 ·2001-09-00 ·Pages 983-92

Klekotka PA, Santoro SA, Ho A, Dowdy SF, Zutter MM

Abstract

The alpha(2)beta(1) integrin supports cell-cycle progression of mammary epithelial cells adherent to type I collagen matrices. Integrin collagen receptors containing the alpha(2) cytoplasmic domain stimulated expression of cyclin E and cyclin-dependent kinase (cdk)2, resulting in cyclin E/cdk2 activation in the absence of growth factors other than insulin. Integrin collagen receptors in which the alpha(2) cytoplasmic domain was replaced by the alpha(1) cytoplasmic domain or an alpha(2) subunit cytoplasmic domain truncated after the GFFKR sequence failed to stimulate cyclin E/cdk2 activation or entry into S phase in the absence of growth factors. Although overexpression of cyclins D or E or cdk2 in cells expressing the integrin collagen receptor with the alpha(1)-integrin cytoplasmic domain did not restore G(1) progression when mammary epithelial cells adhered to type I collagen, co-expression of cyclin E and cdk2 did rescue the ability of the transfectants to enter S phase. Activation of cyclin E/cdk2 complex by mammary epithelial cells required synergy between adhesion mediated by an integrin collagen receptor containing the alpha(2)-integrin subunit cytoplasmic domain and the insulin receptor.

MeSH Terms
Breast/cytology,drug effects CDC2-CDC28 Kinases Cell Cycle/physiology Collagen/pharmacology Cyclin E/metabolism Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases/metabolism Cytoplasm/physiology Drug Synergism Epithelial Cells/metabolism Female Humans Integrins/genetics,physiology Protein Serine-Threonine Kinases/metabolism Receptor, Insulin/physiology Receptors, Collagen S Phase Signal Transduction/physiology Transfection
Chemicals
Cyclin E Integrins Receptors, Collagen Collagen Receptor, Insulin Protein Serine-Threonine Kinases CDC2-CDC28 Kinases CDK2 protein, human Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Klekotka P A
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Santoro S A
Ho A
Dowdy S F
Zutter M M
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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)61774-9
Published
2001-09-00
Pages
983-92
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1850465
Subset
IM
Grants
NCI NIH HHS · CA70275 · United States
NCI NIH HHS · R01 CA083690 · United States
NCI NIH HHS · CA83690 · United States
NHLBI NIH HHS · HL63446 · United States
NCI NIH HHS · R01 CA070275 · United States
External Links
PubMed source DOI: 10.1016/s0002-9440(10)61774-9 PMC Full Text View journal details
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