Bmi-1 extends the life span of normal human oral keratinocytes by inhibiting the TGF-{beta} signaling

Journal Article · Fri Oct 01 00:00:00 EDT 2010 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2010.04.013· OSTI ID:22209904

Lieberman, Mark B.; Lee, Rachel ^[1]; Shin, Ki-Hyuk ^[1]; Mehrazarin, Shebli; Oh, Ju-Eun ^[1]; Park, No-Hee ^[1]

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1. UCLA School of Dentistry, Los Angeles, CA 90095 (United States)

We previously demonstrated that Bmi-1 extended the in vitro life span of normal human oral keratinocytes (NHOK). We now report that the prolonged life span of NHOK by Bmi-1 is, in part, due to inhibition of the TGF-{beta} signaling pathway. Serial subculture of NHOK resulted in replicative senescence and terminal differentiation and activation of TGF-{beta} signaling pathway. This was accompanied with enhanced intracellular and secreted TGF-{beta}1 levels, phosphorylation of Smad2/3, and increased expression of p15{sup INK4B} and p57{sup KIP2}. An ectopic expression of Bmi-1 in NHOK (HOK/Bmi-1) decreased the level of intracellular and secreted TGF-{beta}1 induced dephosphorylation of Smad2/3, and diminished the level of p15{sup INK4B} and p57{sup KIP2}. Moreover, Bmi-1 expression led to the inhibition of TGF-{beta}-responsive promoter activity in a dose-specific manner. Knockdown of Bmi-1 in rapidly proliferating HOK/Bmi-1 and cancer cells increased the level of phosphorylated Smad2/3, p15{sup INK4B}, and p57{sup KIP2}. In addition, an exposure of senescent NHOK to TGF-{beta} receptor I kinase inhibitor or anti-TGF-{beta} antibody resulted in enhanced replicative potential of cells. Taken together, these data suggest that Bmi-1 suppresses senescence of cells by inhibiting the TGF-{beta} signaling pathway in NHOK.

• OSTI ID: 22209904
• Journal Information: Experimental Cell Research, Vol. 316, Issue 16; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
DOSES
IN VITRO
INHIBITION
LIFE SPAN
NEOPLASMS
PHOSPHORYLATION
PROMOTERS
RECEPTORS