Abnormalities in expression of genes, mRNA, and proteins of transforming growth factor-beta receptor type I and type II in human pituitary adenomas.
Abnormalities in the expression of the deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), and proteins of transforming growth factor-beta (TGF-beta) receptor type I (T beta R-I) and TGF-beta receptor type II (T beta R-II) were investigated in 33 human pituitary adenomas. mRNA was extracted from the tumor tissue, and complementary DNA was produced by reverse transcription-polymerase chain reaction (RT-PCR). DNA abnormalities were screened by the PCR method and single-strand conformation polymorphism (SSCP) analysis. Direct sequencing was performed on regions suspected to be abnormal by SSCP (n = 28). The expression of mRNA was measured by quantitative PCR. The expression of T beta R-I and T beta R-II proteins were quantified by immunohistochemical staining. mRNA expression was compared with that of protein expression (n = 22). No gene mutation was detected, but one base substitution in the part of serine/threonine kinase domain of T beta R-II gene (codon 389) was found in 10 of 28 cases examined. Case 2 and case 8 of these 10 cases showed homozygous and heterozygous polymorphism, respectively. The expression of T beta R-I and T beta R-II differed at the protein level between tumors, and was significantly correlated with the expression at the mRNA level. Such differences in the expression of T beta R-I and/or T beta R-II mRNA in pituitary tumors may affect the growth control mediated by TGF-beta, and may indicate the bioactivity of pituitary tumor. Differences in the expression of T beta R-I and/or T beta R-II mRNA are attributable to an abnormality at the transcriptional level.
Fujiwara
K
K
Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan.
Ikeda
H
H
Yoshimoto
T
T
D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005815:Genetic Code; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D014158:Transcription, Genetic
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta