The Journal of Membrane Biology

, Volume 34, Issue 1, pp 1–27 | Cite as

Intercellular communication and tissue growth: VIII. A genetic analysis of junctional communication and cancerous growth

  • R. Azarnia
  • W. R. Loewenstein


Normal, proliferating cells are interconnected at their junctions by membrane channels through which molecules can pass from cell to cell (Loewenstein, W.R. 1966.Ann. N.Y. Acad. Sci.137:708). A channel-competent, normally growing cell (human fibroblast) was hybridized with a channel-incompetent cancer cell (mouse L-1d cell), and the segregant hybrid clones were analyzed in a genetic approach to the question of whether the junctional membrane channels are instrumental in transmission of growth-controlling molecular signals. The channel competence of the human parent was characterized by the ability to transfer small inorganic ions (electrical coupling) and fluorescein, and the growth patterns of this cell, by growthin vitro to low saturation densities and nontumorigenicity in immuno-suppressed hosts. The mouse parent cell had the opposite characteristics. The early hybrid generations (which still had a large part of each parent chromosome complement) were of two classes: one class resembled the human parent cell in channel competence,in vitro growth pattern, and low tumorigenicity within 26 days; the other class presented an intermediate expression of channel competence characterized by transfer of small inorganic ions but not of fluorescein. As the hybrid generations lost human chromosomes, there was segregation of several biochemical and morphological traits, but no segregation of channel competence and normal growth traits. Among the segregants were 22 clones which had reverted to the channel-incompetent trait of the mouse parent. In every case, reversion to the channel defect went hand in hand with reversion to the growth defect, just as, in the early-generation hybrids, correction of the channel defect went hand in hand with correction of the growth defect. Thus, the human genetic factor that corrects the channel defect of the mouse parent cell seems closely linked, if not identical, with that correcting the growth defect. This genetic correlation encourages us in the belief that the channel defect may be an etiological factor in this particular cancer form.


Growth Defect Growth Trait Hybrid Generation Membrane Channel Hybrid Clone 
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Copyright information

© Springer-Verlag New York Inc. 1977

Authors and Affiliations

  • R. Azarnia
    • 1
  • W. R. Loewenstein
    • 1
  1. 1.Department of Physiology and BiophysicsUniversity of Miami School of MedicineMiami

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