RB-mediated tumor suppression of a lung cancer cell line is abrogated by an extract enriched in extracellular matrix.

Published

Journal Article

To examine whether the expression of retinoblastoma (RB) protein could mediate tumor suppression in a lung carcinoma cell line carrying multiple genetic defects, we transfected the Rb gene into a non-small cell lung cancer cell line with absent RB protein. We observed that the stable expression of a functional RB product was associated with a decreased efficiency of soft agar cloning and partial suppression of tumorigenicity in nude mice. The suppression of tumorigenicity was marked when 10(6) cells were injected into the flanks of nude mice but was less prominent when 10(7) cells were injected. RB-mediated tumor suppression, however, was consistently blocked by preincubation of the transfected cells with an extract enriched with an extracellular matrix (Matrigel). Analysis of tumors harvested from nude mice showed that they continued to express detectable levels of human RB protein which retained functional E1A binding activity and nuclear localization. RB-mediated inhibition of soft agar cloning was also blocked in a dose-dependent manner by the addition of Matrigel. These observations demonstrate that the expression of wild-type RB may suppress certain parameters of tumorigenicity in lung carcinoma cells that contain multiple genetic alterations. In addition, the reversal of tumor suppression by an extract enriched in basement membrane components may offer clues for further investigations into the mechanism of RB-mediated tumor suppression.

Full Text

Duke Authors

Cited Authors

  • Kratzke, RA; Shimizu, E; Geradts, J; Gerster, JL; Segal, S; Otterson, GA; Kaye, FJ

Published Date

  • August 1993

Published In

Volume / Issue

  • 4 / 8

Start / End Page

  • 629 - 635

PubMed ID

  • 8398904

Pubmed Central ID

  • 8398904

International Standard Serial Number (ISSN)

  • 1044-9523

Language

  • eng

Conference Location

  • United States