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Multistep Change in Epidermal Growth Factor Receptors during Spontaneous Neoplastic Progression in Chinese Hamster Embryo Fibroblasts¹

Experimental Pathology Group, Life Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545

Whole Chinese hamster embryo lineages have been shown to undergo multistep spontaneous neoplastic progression during serial passage in culture. We have studied the binding, internalization, and degradation of ¹²⁵I-labeled epidermal growth factor at four different stages of transformation. The whole Chinese hamster embryo cells lost cell surface epidermal growth factor receptors gradually during the course of neoplastic progression until only 10% of the receptor number present in the early-passage cells (precrisis) were retained in the late-passage cells (tumorigenic). No differences in internalization rates, chloroquine sensitivity, or ability to degrade hormone between the various passage levels were seen. No evidence for the presence in conditioned medium of transforming growth factors which might mask or down-regulate epidermal growth factor receptor was obtained. These results suggest that a reduction in cell surface epidermal growth factor receptor might be an early event during spontaneous transformation in whole Chinese hamster embryo cells.

¹ This work was performed under the auspices of the United States Department of Energy.

² To whom requests for reprints should be addressed, at LS-4, M.S. M888, Los Alamos National Laboratory, Los Alamos, NM 87545.

Received 6/18/84. Revised 10/15/84. Revised 1/22/85. Accepted 1/29/85.