T-cadherin upregulation correlates with cell-cycle progression and promotes proliferation of vascular cells.
OBJECTIVE
In vascular tissue, T-cadherin (T-cad) levels correlate with the progression of atherosclerosis, restenosis and tumour neovascularization. This study investigates whether T-cad influences proliferation of vascular cells.


RESULTS
Cultures of human umbilical vein endothelial cells (HUVEC) and rat and human aortic smooth muscle cells (rSMC, hSMC) were used. T-cad was overexpressed in HUVEC and hSMC using an adenoviral expression system. In cultures released from G(1)/G(0) synchrony parallel immunoblot analysis of T-cad and cell cycle phase specific markers (p27(Kip1), cyclin D1, E2F1, PCNA, cyclin B) showed increased T-cad protein levels subsequent to entry into early S-phase with sustained elevation through S-and M-phases. T-cad was increased in G(2)/M-phase (colchicine) synchronized cultures. In FACS-sorted cell populations, expression of T-cad in S-and G(2)/M-phase was higher than G(1)/G(0)-phase. Compared with empty-and LacZ-vector infected controls, HUVEC and hSMC overexpressing T-cad exhibited increased proliferation as assessed in enumeration and DNA synthesis assays. Additionally, following release from G(1)/G(0) synchrony, HUVEC and hSMC overexpressing T-cad enter S-phase more rapidly. Flow cytometry after BrdU/propidium labelling confirmed increased cell cycle progression in T-cad overexpressing cells.


CONCLUSIONS
In vascular cells, T-cad is dynamically regulated during the cell cycle and its expression functions in the promotion of proliferation. T-cad may facilitate progression of proliferative vascular disorders such as atherosclerosis, restenosis and tumour angiogenesis.
Ivanov
Danila
D
Department of Research, Cardiovascular Laboratories, Basel University Hospital, ZLF 316, Hebelstrasse 20, CH 4031 Basel, Switzerland.
Philippova
Maria
M
Allenspach
Roy
R
Erne
Paul
P
Resink
Thérèse
T
D000818:Animals; D001011:Aorta; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D051381:Rats; D014161:Transduction, Genetic / Q000379:methods; D014471:Umbilical Veins
D015820:Cadherins; C099972:H-cadherin