Regular Article

British Journal of Cancer (2000) 83, 519–525. doi:10.1054/bjoc.2000.1257 www.bjcancer.com
Published online 25 July 2000

Down-regulation of TGF-bold beta 1 production restores immunogenicity in prostate cancer cells

E Matthews1, T Yang1, L Janulis1, S Goodwin1, S D Kundu1, W J Karpus2 and C Lee1

  1. 1Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA
  2. 2Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA

Received 7 December 1999; Revised 22 March 2000; Accepted 26 March 2000.

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Abstract

The objective of this study is to determine if a non-immunogenic Dunning's rat prostate cancer cell line, MATLyLu, can become immunogenic by reducing the endogenous production of TGF-beta1. An expression construct containing a DNA sequence in an antisense orientation to TGF-beta1 (TGF-beta1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-beta1 reduced from 70 to10 pg per 2 times 104cells and the rate of in vitro3H-thymidine incorporation increased 3–5-fold. After subcutaneous injection of tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the control construct, but only 43% (9/21, Pless than or equal to 0.05) for cells transfected with TGF-beta1 antisense. However, when cells were injected into immunodeficient hosts (athymic nude rats), the incidence of tumour development was 100% (10/10) for both the wild type MATLyLu cells and cells transfected with the control construct and 90% (9/10) for cells transfected with TGF-beta1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-beta1 is down-regulated. © 2000 Cancer Research Campaign

Keywords:

TGF-beta, expression, rat prostate cancer, immunogenicity, tumour incidence, host–tumour interaction

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