Adrenergic receptor as a proto-oncogene

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

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4352401, C12Q 168, C12N 510

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active

055739083

ABSTRACT:
A recombinant cell comprising a host cell containing a recombinant DNA sequence is disclosed. The recombinant DNA sequence comprises vector DNA and DNA which encodes a mammalian adrenergic receptor. The host cell is one capable of undergoing proliferation in response to activation of the adrenergic receptor. In one specific embodiment of the foregoing, the adrenergic receptor includes a mutation in the third cytoplasmic loop thereof which renders the adrenergic receptor constitutively active, and the host cell undergoes proliferation in response to the constitutively active adrenergic receptor. Also disclosed are in vitro assays employing the foregoing which are useful for screening test compounds for antitumor and antiatherogenic activity, along with a diagnostic assay for detecting the oncogenic activation of cells in a patient. The diagnostic assay comprises collecting sample cells which express adrenergic receptors from the patient, and then detecting the presence or absence of a mutation in the adrenergic receptor which renders the receptor constitutively active. The presence of such a mutation indicates the oncogenic activation of the cells.

REFERENCES:
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Schuller, H. M. (1989) Carcinogenesis, vol. 10, No. 9, pp. 1753-1755.
Cotecchia, S. et al. (1988) Proceedings of the National Academy of Sciences, vol. 85, pp. 7159-7163.
D. Julius et al., Science 244, 1057-1062 (1989).
D. Young et al., Cell 45, 711-719 (1986).
J. Gutkind et al., Proc. Natl. Acad. Sci. USA 88, 4703-4707 (1991).
S. Cotecchia et al., Proc. Natl. Acad. Sci. USA 87, 2896-2900 (1990).

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