Matrigel-induced acinar differentiation is followed by apoptosis in HSG cells.
It has been shown that a human salivary gland cell line (HSG) is capable of differentiation into gland-like structures, though little is known of how morphological features are formed or controlled. Here we investigated the changes in cell proliferation and apoptosis upon terminal differentiation of HSG cells in Matrigel, an extracellular matrix derivative. Changes in the expression of survivin, a prominent anti-apoptotic factor, and caspase-3, a key apoptotic factor were also measured. In order to better understand the involvement of key signal transduction pathways in this system we pharmacologically blocked the activity of tyrosine kinase, nuclear factor kappa B(NF kappa B), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K) and matrix metalloproteases (MMP). Results of these studies demonstrate that cytodifferentiation of HSG cells to an acinar phenotype is accompanied first by a decrease of cell proliferation and then by a massive programmed cell death, affected by multiple signal transduction pathways. Thus, Matrigel alone is insufficient for the full maturation and long term survival of the newly formed acini: the presence of other factors is necessary to complete the acinar differentiation of HSG cells.
Szlávik
Vanda
V
Molecular Oral Biology Research Group, Department of Oral Biology, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary.
Vág
János
J
Markó
Károly
K
Demeter
Kornél
K
Madarász
Emília
E
Oláh
Imre
I
Zelles
Tivadar
T
O'Connell
Brian C
BC
Varga
Gábor
G
D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004338:Drug Combinations; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007797:Laminin / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000494:pharmacology*; D012469:Salivary Glands / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin
D017302:Annexins; C107489:BIRC5 protein, human; D004338:Drug Combinations; D051034:Inhibitor of Apoptosis Proteins; D007797:Laminin; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011509:Proteoglycans; D000077022:Survivin; C059485:matrigel; D003094:Collagen; D004247:DNA; D053148:Caspase 3