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Increased Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor and Transforming Growth Factor ß1 Levels during Monoterpene-induced Regression of Mammary Tumors¹

Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 [R. L. J.]); and Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin 53792 [J. D. H., E. A. A., M. N. G.]

The monoterpenes represent a potentially new class of breast cancer therapeutic agents. We have shown that d-limonene induces the regression of advanced rat mammary adenocarcinomas. These regressing tumors have an increased cellular concentration of both the mannose-6-phosphate/insulin-like growth factor II receptors and transforming growth factor ß1. The terpene-induced regression of mammary tumors may result in part from the mitoinhibitory and differentiation properties of active transforming growth factor ß1. Furthermore, the activation of transforming growth factor ß1 in these tumors is likely to be facilitated by the increased concentration of the mannose-6-phosphate/insulin-like growth factor II receptors in the mammary tumor cells. Tumors not responding to terpene therapy lacked a rise in the mannose-6-phosphate/insulin-like growth factor II receptor level which may relate to the fact that this gene is hemizygous due to maternal imprinting.

¹ This work was supported by PHS NIH Grants CA25951 and CA40172 (R. L. J.) and CA38128 (M. N. G.).

² To whom requests for reprints should be addressed, at Box 3433, Duke University Medical Center, Durham, NC 27710.

Received 6/15/93. Accepted 7/21/93.

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