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Transforming Growth Factor and ß Expression in Human Colon Cancer Lines: Implications for an Autocrine Model¹

Departments of Cell Biology [R. J. C., J. W., H. L. M.], Biochemistry [A. M. S., G. C.], and Medicine [R. J. C.], Vanderbilt University, Nashville, Tennessee 37232, and Department of Cell Biology [A. S. G., G. D. S.], Mayo Clinic, Rochester, Minnesota 55905

Three human colon cancer lines (SW480, SW620, WIDR) secrete different levels of transforming growth factor ß (TGFß)-like and transforming growth factor (TGF)/epidermal growth factor (EGF)-like molecules into serum-free conditioned media as measured by competing activity in TGFß and EGF radioreceptor assays. SW480 cells, the highest producers of TGFß-like activity, lack detectable TGFß receptors while SW620 cells, the highest producers of TGF/EGF-like activity, lack EGF receptors. This study investigated the production of these growth factors at the mRNA level and examined the mechanism of loss of detectable receptors. Using complementary DNA probes for TGFß and TGF, it was demonstrated that mRNA levels correlated with the amounts of TGFß and TGF produced; TGFß gene expression was highest in SW480 cells and TGF gene expression was highest in SW620 cells. Acid washing of the SW480 cells prior to performing the TGFß binding assay resulted in the unmasking of substantial levels of TGFß receptors. Neither acid washing nor preincubation with suramin uncovered EGF receptors in SW620 cells. Also, and in contrast to the other two lines, EGF receptor expression could not be detected in SW620 cells by Northern gel analysis of receptor messenger RNA or by immunological analysis of receptor protein. Thus two distinct mechanisms (occupation of TGFß receptor in SW480 cells, or absence of EGF receptor in SW620 cells) explain the lack of detectable TGFß and EGF receptors in the binding assays. The autocrine hypothesis remains viable for TGFß in SW480 cells but not for TGF in SW620 cells; this would not discount a paracrine role in this latter case.

¹ This investigation was supported by USPHS grants CA42572, CA42749, CA42750 (H. L. M.); CA24071 (A. M. S., G. C.); and CA42409 (G. D. S.).

² Present address: Center for Blood Research, Boston, MA 02115.

³ Present address: Department of Cell Biology and Anatomy, Oregon Health Sciences, Portland, OR 97201.

⁴ To whom requests for reprints should be addressed.

Received 3/ 6/87. Revised 5/26/87. Accepted 6/ 2/87.

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