The association of the H-ras oncogene and steroid hormone receptors in gynecological cancer.
Expression of the ras family of cellular oncogenes is associated with tumorigenicity, invasiveness and metastatic potential in a variety of human carcinomas. Additionally, H-ras cooperates with glucocorticoids and with ovarian hormones in cell transformation and in the development of mammary carcinomas. Steroids are considered to be tumor promoters and their levels influence the cure rates and survival of the patients with gynecological lesions. It is proposed that they exert tumor promoting activity by transcriptional regulation of nuclear proto-oncogenes, such as c-fos, c-jun, and c-myc. The human H-ras gene contains within its first and fourth introns, sequences that are specifically recognized by glucocorticoid and estrogen receptors, respectively. Using gel retardation assays, the level of steroid receptor binding in H-ras elements has been compared, employing nuclear extracts from human endometrial and ovarian lesions and from the adjacent normal tissue. Elevated binding of the glucocorticoid and estrogen receptors in the corresponding H-ras elements in almost all tissue pairs tested has been found. It is suggested that the H-ras proto-oncogene is hormonally regulated and directly implicated in human gynecological cancer through elevated, steroid-induced gene expression.
Zachos
G
G
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Varras
M
M
Koffa
M
M
Ergazaki
M
M
Spandidos
D A
DA
D005260:Female; D011905:Genes, ras / Q000235:genetics* / Q000502:physiology*; D005833:Genital Neoplasms, Female / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D000090063:Proto-Oncogene Mas; D011987:Receptors, Steroid / Q000235:genetics* / Q000502:physiology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011987:Receptors, Steroid