Cyclic AMP specifically blocks proliferation of rat 3T3 cells transformed by polyomavirus

Elevated exogenous and intracellular levels of cyclic AMP could totally block proliferation of polyomavirus (PyV) transformants derived from rat 3T3 cells without affecting proliferation of normal cells or simian virus 40 (SV40)-induced transformants. Concanavalin A (ConA) had the opposite effect; it could totally block proliferation of both normal cells and SV40 transformants but reduced proliferation of PyV transformants only twofold. Adenylate cyclase was threefold less active in membranes of PyV transformants, and the number of ConA receptors was similar to that of normal cells. Proliferating PyV transformants contained threefold less cyclic AMP than did proliferating SV40 transformants. The sensitivity to cyclic AMP did not correlate with the degree of transformation: cells transformed by Rous sarcoma virus and tumor cells derived from SV40 transformants were not sensitive to cyclic AMP. The differential effect of cyclic AMP and ConA on proliferation was probably due to the activity of an intact middle t protein. The presence of both large T and small t together with middle t was also required for cyclic AMP sensitivity.

[1]  Y. Nishizuka,et al.  [The role of protein kinase C in cell surface signal transduction and tumor promotion]. , 1986, Gan to kagaku ryoho. Cancer & chemotherapy.

[2]  I. Pastan,et al.  Cholera toxin treatment stimulates tumorigenicity of Rous sarcoma virus-transformed cells , 1984, Molecular and cellular biology.

[3]  C. Heldin,et al.  Growth factors: Mechanism of action and relation to oncogenes , 1984, Cell.

[4]  R. Weinberg,et al.  Cellular oncogenes and multistep carcinogenesis. , 1983, Science.

[5]  Alan E. Smith,et al.  Polyoma virus transforming protein associates with the product of the c-src cellular gene , 1983, Nature.

[6]  Isabelle,et al.  Rat cells transformed by simian virus 40 give rise to tumor cells which contain no viral proteins and often no viral DNA , 1983, Molecular and cellular biology.

[7]  A. Zachowski,et al.  Stimulation by tubulin of an adenylate cyclase from murine plasmacytoma. , 1981, European journal of biochemistry.

[8]  E. Rozengurt,et al.  Cyclic AMP: a mitogenic signal for Swiss 3T3 cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R. Seif,et al.  Factors which disorganize microtubules or microfilaments increase the frequency of cell transformation by polyoma virus , 1980, Journal of virology.

[10]  R. Seif Polyoma virus middle t antigen: a tumor progression factor , 1980, Journal of virology.

[11]  Y. Ito,et al.  Middle T antigen as primary inducer of full expression of the phenotype of transformation by polyoma virus , 1980, Journal of virology.

[12]  R. Martin,et al.  Simian virus 40 small t antigen is not required for the maintenance of transformation but may act as a promoter (cocarcinogen) during establishment of transformation in resting rat cells , 1979, Journal of virology.

[13]  B. Griffin,et al.  New classes of viable deletion mutants in the early region of polyoma virus , 1979, Journal of virology.

[14]  H. Green,et al.  Cyclic AMP in relation to proliferation of the Epidermal cell: a new view , 1978, Cell.

[15]  F. Cuzin,et al.  Temperature-sensitive growth regulation in one type of transformed rat cells induced by the tsa mutant of polyoma virus , 1977, Journal of virology.

[16]  T. Puck,et al.  Cyclic AMP, the microtubule-microfilament system, and cancer. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Edelman,et al.  Analysis of the stimulation-inhibition paradox exhibited by lymphocytes exposed to concanavalin A , 1976, The Journal of experimental medicine.

[18]  G M Edelman,et al.  Surface modulation in cell recognition and cell growth. , 1976, Science.

[19]  G. Edelman,et al.  Modulation of lymphocyte mitogenesis. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[20]  T. Puck,et al.  Membrane dynamics in the action of dibutyryl adenosine 3':5'-cyclic monophosphate and testosterone on mammalian cells. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Sheppard Restoration of contact-inhibited growth to transformed cells by dibutyryl adenosine 3':5'-cyclic monophosphate. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[22]  T. Puck,et al.  Morphological transformation of Chinese hamster cells by dibutyryl adenosine cyclic 3':5'-monophosphate and testosterone. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[23]  U. Zor,et al.  Role of cytoskeletal organization in the regulation of adenylate cyclase-cyclic adenosine monophosphate by hormones. , 1983, Endocrine reviews.

[24]  J. Bishop Cellular oncogenes and retroviruses. , 1983, Annual review of biochemistry.

[25]  T. Slaga,et al.  Mechanisms of tumor promotion and cocarcinogenesis , 1978 .

[26]  G. S. Johnson,et al.  Role of cyclic nucleotides in growth control. , 1975, Annual review of biochemistry.

[27]  G. Brooker,et al.  Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution. , 1975, Journal of cyclic nucleotide research.