Published in Cancer Detection and Prevention 1997; 21(4):289-294.

Elimination of Intercellular Junctional Communication Requires Lower Ras 1eu61 Levels Than Stimulation of Anchorage-Independent Proliferation

Heather L Brownell^a, James F Whitfield^b, Leda Raptis^a

Address all correspondence and reprint requests to: Leda Raptis, Departments of Microbiology and Immunology and Pathology, Queen's University, Kingston, Ontario, K7L 3N6. Canada.

ABSTRACT: One of the effects of transformation by a variety of factors is a decrease in gap junctional, intercellular communication (GJIC). To investigate the role of the Ras oncogene product in gap junction closure, and to incorporate GJIC into the gamut of transformation-related properties which can be regulated by increasing levels of oncogene expression, a panel of murine C3H10T1/2 and 3T3Ll fibroblasts was constructed in which graded increments of Ras 1eu61 could reliably be obtained. The inducibly activated Ras 1eu61 protein substantially reduced or eliminated GJIC at levels much lower than those needed for neoplastic transformation, as indicated by acquisition of the ability to proliferate in the absence of anchorage. These results indicate that disruption of GJIC, although necessary, is not sufficient for neoplastic transformation in this system.

KEY WORDS: anchorage-independent proliferation, intercellular junctional communication, neoplastic transformation, Ras oncogene.

http://www.cancerprev.org/Journal/Issues/21/4/200