PMID- 11879577
OWN - NLM
STAT- MEDLINE
DCOM- 20020327
LR  - 20181130
IS  - 1044-5498 (Print)
IS  - 1044-5498 (Linking)
VI  - 21
IP  - 1
DP  - 2002 Jan
TI  - Morphologic change and elevation of cortisol secretion in cultured human normal 
      adrenocortical cells caused by mutant p21K-ras protein.
PG  - 21-9
AB  - In our previous study on the tumorigenesis of human functional adrenal tumors, we 
      observed a high frequency of K-ras point mutations in clinical specimens. 
      Furthermore, we cloned the mutated K-ras gene from the tumors and inserted it 
      into vectors to transfect normal bovine adrenocortical cells to express the 
      mutated K-ras gene. The mRNA level of steroidogenic enzymes such as cholesterol 
      sidechain cleavage enzyme (P450SCC), 17alpha-hydroxylase/17,20-lyase (P450c17), 
      and 3beta-hydroxysteroid dehydrogenase (3betaHSD) in the mutant K-ras stably 
      transfected cells were elevated. Cultured normal adrenocortical cells from donors 
      and patients with adrenocortical tumors were then transfected with mutant K-ras 
      expression plasmids constructed from human adrenal tumors. Stable transfectants 
      grew faster than normal cells. Additionally, morphologic change was observed in 
      the transfected cells. Moreover, when the synthesis of hormones was analyzed, the 
      mRNA of P450SCC, P450C17, and 3betaHSD was found to have increased, and the level 
      of cortisol was 18 to 25 times that in control cells. The increased steroid 
      hormone production in mutant K-ras-transfected cells was reversed by lovastatin, 
      a pharmacologic inhibitor of p21ras function. These results, combined with 
      previous reports of steroidogenic K-ras in bovine adrenocortical cells, suggest 
      that the K-ras oncogene is involved in steroidogenesis in human adrenocortical 
      cells.
FAU - Wu, Chia-Hung
AU  - Wu CH
AD  - Graduate Institute of Biochemistry, Kaohsiung Medical University Kaohsiung, 
      Taiwan, ROC.
FAU - Lee, Su-Chen
AU  - Lee SC
FAU - Chiu, Hua-Hsien
AU  - Chiu HH
FAU - Yang, Yuan-Chieh
AU  - Yang YC
FAU - Lian, Shen-Tsuen
AU  - Lian ST
FAU - Shin, Shyi-Jang
AU  - Shin SJ
FAU - Lin, Shiu-Ru
AU  - Lin SR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - DNA Cell Biol
JT  - DNA and cell biology
JID - 9004522
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 4964P6T9RB (Aldosterone)
RN  - 9LHU78OQFD (Lovastatin)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adrenal Cortex/*metabolism/pathology
MH  - Aldosterone/metabolism
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Division
MH  - Cells, Cultured
MH  - Cholesterol Side-Chain Cleavage Enzyme/genetics/metabolism
MH  - Humans
MH  - Hydrocortisone/*metabolism
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
MH  - Hydroxysteroid Dehydrogenases/genetics/metabolism
MH  - Lovastatin/pharmacology
MH  - *Point Mutation
MH  - Proto-Oncogene Proteins p21(ras)/*physiology
MH  - RNA, Messenger/metabolism
MH  - Transfection
MH  - Up-Regulation
EDAT- 2002/03/07 10:00
MHDA- 2002/03/28 10:01
CRDT- 2002/03/07 10:00
PHST- 2002/03/07 10:00 [pubmed]
PHST- 2002/03/28 10:01 [medline]
PHST- 2002/03/07 10:00 [entrez]
AID - 10.1089/10445490252810285 [doi]
PST - ppublish
SO  - DNA Cell Biol. 2002 Jan;21(1):21-9. doi: 10.1089/10445490252810285.