Open AccessAllelic Loss at the Tuberous Sclerosis ( Tsc2 ) Gene Locus in Spontaneous Uterine Leiomyosarcomas and Pituitary Adenomas in the Eker Rat Model
Author(s) -
Kubo Yoshiaki,
Kikuchi Yasushi,
Mitani Hiroaki,
Kobayashi Etsuko,
Kobayashi Toshiyuki,
Hino Okio
Publication year - 1995
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1995.tb03092.x
Subject(s) - tsc2 , tuberous sclerosis , loss of heterozygosity , tumor suppressor gene , locus (genetics) , carcinogenesis , allele , biology , adenoma , tsc1 , endocrinology , cancer research , pituitary gland , medicine , pathology , gene , hormone , genetics , pi3k/akt/mtor pathway , apoptosis
Hereditary renal carcinomas (RCs) develop in virtually all Eker rats by the age of one year. Investigation of extra‐renal primary tumors co‐occurring in Eker rats late in life (at 2 years) additionally revealed enhanced development of hemangiosarcomas of the spleen, uterine leiomyosarcomas and pituitary adenomas, although the demonstrated predilection for these extra‐renal tumors was not as complete as with RCs. We identified the germline mutated tuberous sclerosis ( Tsc2 ) gene as the predisposing Eker gene and revealed the tumor suppressor nature of Tsc2 gene function in renal carcinogenesis. In the present study, we examined allelic loss at the Tsc2 gene locus in uterine leiomyosarcomas and pituitary adenomas developing in hybrid F1 rats carrying the Eker mutation as well as in pituitary adenomas from non‐carrier rats. We detected loss of heterozygosity in 4 of 11 uterine leiomyosarcomas (36%) and 11 of 31 pituitary adenomas (35%) from Eker rats but in none of 9 pituitary adenomas from non‐carrier rats ( P <0.05), suggesting that inactivation of the Tsc2 gene is also a critical event in the pathogenesis of these extra‐renal tumors. Our present data indicate that there might be different pathways for tumorigenesis of pituitary adenomas between Eker and non‐carrier rats.