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Anti-IgM Induces Transforming Growth Factor+ Sensitivity in a Human B-Lymphoma Cell Line: Inhibition of Growth Is Associated With a Downregulation of Mutant p53
Blood (1995)
  • Margaret Beckwith, National Institutes of Health
  • Francis W. Ruscetti, National Institutes of Health
  • Garwin K. Sing, National Institutes of Health
  • Walter J. Urba, Providence Portland Medical Center
  • Dl Longo, Science Applications International Corporation
Abstract
We wished to examine the role of transforming growth factor+ (TGF-p) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-p, and thus has lost the ability to respond to the inhibitory dects of TGF-j?. We demonstrate here that anti-lg antibodies can efficiently upregulate the expression of TGF-p receptors and promote sensitivity to growth inhibition by TGF-p. Furthermore, because TGF-/3 has been shown to function in late G, of the cell cycle, we examined the a b i l i of TGF-j? to modulate two tumor suppressor proteins known to be critical regulators of the Gl/S transition, Rb and p53. Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53 kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-p treatment of phorbol myristate acetate (PMA) or anti-lg-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-j? treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53. We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-ptr eatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-j?, the ability of TGF-p to induce apoptosis must be independently controlled.
Disciplines
Publication Date
May 1, 1995
Citation Information
Margaret Beckwith, Francis W. Ruscetti, Garwin K. Sing, Walter J. Urba, et al.. "Anti-IgM Induces Transforming Growth Factor+ Sensitivity in a Human B-Lymphoma Cell Line: Inhibition of Growth Is Associated With a Downregulation of Mutant p53" Blood Vol. 85 Iss. 9 (1995) p. 2461 - 2470 ISSN: 0006-4971
Available at: http://works.bepress.com/walter-urba/182/