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Comparison of Mouse pro-1 and pro-2 Transfectants for Responses to Tumor Promoters and Antipromoters¹

Cell Biology Section, Laboratory of Viral Carcinogenesis, National Cancer Institute [N. H. C., B. M. S., Y. N.], and Biological Carcinogenesis Development Program, Program Resources Inc., NCI-Frederick Cancer Research Facility [E. J. W., D. W.], Frederick, Maryland 21701

A previous report demonstrated that mouse JB6 cells transformed to promotion sensitive (P⁺) phenotype by transfection with an activated promotion sensitivity (pro) gene showed both evidence for the presence of the transfected gene and sensitivity to phorbol ester induced transformation similar to that observed in parental P⁺ cells. In addition, pro-1 and pro-2 transfectants were similar to each other in phorbol ester response. The current report extends these findings to ask whether pro-1 or pro-2 transfectants are also sensitive to promotion of transformation by other classes of tumor promoters such as epidermal growth factor (EGF), lanthanides, and phthalate esters and to inhibition of phorbol ester promoted transformation by several classes of antipromoters.

The results showed that both pro-1 and pro-2 transfectants resembled parental P⁺ cells in sensitivity to promotion of anchorage independent transformation by lanthanides and by diethylhexylphthalate. In addition both pro-1 and pro-2 transfectants showed inhibition of phorbol ester induced transformation by antipromoters ganglioside G_T1b, ethylene glycol bis(ß-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and forskolin. Thus the pathways implicated by these inducers and inhibitors of transformation appear similar to those implicated for parental P⁺ cells and similar when controlled by pro-1 or pro-2. The single differential response was that of EGF-induced transformation. pro-2 transfectants but not pro-1 transfectants were sensitive to EGF-induced neoplastic transformation. The nonresponsiveness could not be attributed to lack of EGF receptors since ¹²⁵I-EGF binding to pro-1 transfectants was similar to that for pro-2 transfectants and parental P⁺ cells. Thus pro genes transfer responsiveness to a C-kinase mediated promotion of transformation pathway and to putatively non-C kinase pathways triggered by lanthanides or phthalate esters, but not necessarily to an EGF receptor kinase mediated pathway.

¹ This project has been funded in part with Federal funds from the Department of Health and Human Services under Contract NO1-CO-74102 with Program Resources, Inc. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. Y. Nakamura was supported by a Cancer Research Campaign International Fellowship from the International Union against Cancer and by a Foreign Study Grant from the Ministry of Education, Science and Culture of Japan. B. Smith was supported in part by National Research Service Award F32 ESO 5305.

² To whom requests for reprints should be addressed, at NCI-FCRF, Bldg. 560, Room 21-89B, Frederick, MD 21701-1013.

³ Present address: Laboratory of Health Science, Shizuoka College of Pharmaceutical Sciences, Shizuoka, Japan.

Received 1/26/85. Revised 6/29/88. Accepted 8/ 4/88.

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