PMID- 10822234
OWN - NLM
STAT- MEDLINE
DCOM- 20000802
LR  - 20190905
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 142
IP  - 6
DP  - 2000 Jun
TI  - Multiple endocrine neoplasia type 1 gene expression is normal in sporadic 
      adrenocortical tumors.
PG  - 689-95
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with 
      neoplasia of the anterior pituitary, the parathyroid, the endocrine pancreas and 
      other endocrine tissues including the adrenal cortex. The tumor-suppressor gene 
      causing this disease was identified at the gene locus 11q13. We recently reported 
      that adrenocortical carcinomas frequently show loss of heterozygosity (LOH) of 
      11q13, but do not contain point mutations within the MEN1-coding region. To 
      investigate whether reduced gene expression (for example by mutations within the 
      MEN1 promoter) may contribute to the tumorigenesis of sporadic adrenocortical 
      tumors, 24 adrenocortical specimen were studied by Northern blot analysis. This 
      series included six adrenocortical carcinomas, four cortisol-producing adenomas, 
      six aldosterone-producing adenomas, three endocrine-inactive adenomas and six 
      normal adrenal glands. The presence of LOH of 11q13 was investigated using five 
      polymorphic microsatellite markers (D11S956, PYGM, D11S4939, D11S4946 and 
      D11S987) close to the MEN1 gene. Poly-A mRNA was hybridized with a PCR-generated 
      cDNA probe of the MEN1 gene, a cDNA of the former MEN1 candidate gene 
      phospholipase (PLC) beta3 and a mouse beta-actin cDNA for normalization. LOH of 
      11q13 was detected in five out of six carcinomas and two inactive adenomas, but 
      in none of the hormone-producing adenomas. Compared with normal adrenals 
      (100+/-6. 5%, mean+/-s.e.m.) MEN1 mRNA in adrenocortical tumors was expressed in 
      similar amounts (carcinomas 109+/-11%, cortisol-producing adenomas 131+/-10%, 
      aldosterone-producing adenomas 113+/-13%, endocrine-inactive adenomas 111+/-2%) 
      with the exception of one adrenocortical carcinoma with low MEN1 mRNA expression 
      (66%). PLCbeta3 mRNA expression showed a variable pattern without reaching 
      significant differences between the groups. We conclude that since mRNA levels 
      were unaltered in the majority of tumors, mutations of the MEN1 gene causing 
      altered gene transcription is unlikely to be a major pathogenic factor of 
      sporadic adrenocortical tumors.
FAU - Zwermann, O
AU  - Zwermann O
AD  - Clinic for Endocrinology and Metabolism, University of Mainz, Germany.
FAU - Beuschlein, F
AU  - Beuschlein F
FAU - Mora, P
AU  - Mora P
FAU - Weber, G
AU  - Weber G
FAU - Allolio, B
AU  - Allolio B
FAU - Reincke, M
AU  - Reincke M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (RNA, Messenger)
RN  - 4964P6T9RB (Aldosterone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adenoma/genetics/*metabolism
MH  - Adrenal Cortex Neoplasms/genetics/*metabolism
MH  - Adrenal Glands/metabolism
MH  - Aldosterone/biosynthesis
MH  - Carcinoma/genetics/*metabolism
MH  - *Gene Expression
MH  - Humans
MH  - Hydrocortisone/biosynthesis
MH  - Loss of Heterozygosity
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - RNA, Messenger/metabolism
MH  - Reference Values
EDAT- 2000/05/24 09:00
MHDA- 2000/08/06 11:00
CRDT- 2000/05/24 09:00
PHST- 2000/05/24 09:00 [pubmed]
PHST- 2000/08/06 11:00 [medline]
PHST- 2000/05/24 09:00 [entrez]
AID - 1420689 [pii]
AID - 10.1530/eje.0.1420689 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2000 Jun;142(6):689-95. doi: 10.1530/eje.0.1420689.