No evidence for oncogenic mutations in guanine nucleotilde-binding proteins of endocrine tumors

ABSTRACT

In recent years, the application of DNA technology has led to significant advances in the elucidation of the somatic defects which can occur in several tumors, including oncogene expression, allelic loss and inappropriate gene transcription and translation. Normal cell growth is regulated by many proto-oncogenes encoding proteins and specific mutations can convert these genes in oncogenes, leading to abnormal protein products that are responsible for the growth of malignant cells. Mutations that inhibit GTPase activity of the a subunit of the stimulatory G protein (Gsa) have been demonstrated in approximately a thrid of GH-secreting tumors, in 10 percent of functionless pituitary tumors, and also in corticotropinomas although with far less frequency. These mutations -gsp mutations - stabilize the Gsa in the active state (GTP-bound state), resulting in the permanent activation of adenylyl cyclase, leading to tumorigenesis. In addition, mutations in the a subunit of the inhibitory GTP-binding protein gene (Gi2a), or gip mutations, have been found in a subset of adrenocortical and ovarian tumors. In the present work, using the polymerase chain reaction and denaturing gradient gel electrophoresis, we investigated the existence of gsp and gip mutations in twenty three different endocrine tumors.