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Enhanced Expression of c-myc and Decreased Expression of c-fos Protooncogenes in Chemically and Radiation-transformed C3H/10T1/2 Cl 8 Mouse Embryo Cell Lines¹

Departments of Microbiology [J. R. L.] and Pathology [J. R. L., P. R-B.], Norris Cancer Hospital and Research Institute [T. S., S. R. P., P. C. B., J. R. L.], Comprehensive Cancer Center, University of Southern California, School of Medicine, Los Angeles, California 90033

c-abl, c-fos, c-Ha-ras, c-myc, and c-mos were expressed whereas c-sis, c-fms, c-rel, c-src, and c-myb expression was not detectable in C3H/10T1/2 Cl 8 (10T1/2) cells and in eight chemically and radiation-transformed 10T1/2 cell lines. The expression of c-abl, c-fos, c-Ha-ras, and c-myc was growth-related in nontransformed 10T1/2 cells. c-abl and c-fos expression increased at confluence by 5- and 9-fold, respectively, compared to that in log phase cells. c-Ha-ras and c-myc transcripts were most abundant in log phase cells and decreased by 70 and 50%, respectively, in confluent cells. There were no significant growth-related changes in the expression of c-Ha-ras, c-myc, or c-abl in methylcholanthrene-transformed Cl 15 cells. The c-fos transcript was not detected in Cl 15 cell cultures.

c-abl, c-fos, c-ras, and c-myc were expressed in whole C3H mouse embryo tissue, mouse liver, and 10T1/2 cells. Sizes of these protooncogene transcripts in 10T1/2 cells were the same as those in whole embryo tissue, except that 10T1/2 cells did not express the 8.2-kilobase abl transcript.

At subconfluence, equivalent low levels of c-mos expression were observed in nontransformed and in the eight transformed 10T1/2 cell lines. The level of c-abl expression was similar in the nontransformed and in the eight transformed cell lines, but there was a new 8.2-kilobase transcript in the transformed MCA Cl 15 cell line. c-fos was expressed in 10T1/2 cells but was not detectable or greatly reduced in eight transformed cell lines. c-Ha-ras was expressed to a similar extent in eight transformed cell lines and in nontransformed 10T1/2 cells. In the UVC-4 transformed cell line, extra 3.3-kilobase Ha-ras and 7.5-kilobase Ki-ras transcripts were observed. c-myc was expressed at 4- to 7-fold higher levels in six transformed cell lines compared to 10T1/2 cells. There were no major rearrangements in or amplification of the c-myc gene in three transformed cells overexpressing this gene 5-fold.

These studies show that enhanced expression of c-myc and decreased expression of c-fos correlate with the chemically and radiation transformed states of 10T1/2 cells. Changes in c-fos and c-myc oncogene expression may be causally linked to late stages of neoplastic transformation in these chemically and radiation transformed 10T1/2 cell lines.

¹ This work was supported by Grant ES03341 from NIH, by a grant from the R. J. Reynolds Co., and by an Occupational and Environmental Health Grant from the DuPont Co. to Joseph R. Landolph.

² Present address: Department of Urology, Yokohama City University Hospital, 3-46 Urafune-cho Minami-ku, Yokohama, Kanagawa, Japan.

³ Present address: Department of Cancer Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115.

⁴ Present address: Department of Biochemistry, University of Bergen, Norway.

⁵ To whom requests for reprints should be addressed.

Received 5/17/85. Revised 6/16/86. Accepted 7/ 2/86.

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