PMID- 15026366
OWN - NLM
STAT- MEDLINE
DCOM- 20040408
LR  - 20191108
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 6
DP  - 2004 Mar 15
TI  - Menin inactivation leads to loss of transforming growth factor beta inhibition of 
      parathyroid cell proliferation and parathyroid hormone secretion.
PG  - 2222-8
AB  - Primary hyperparathyroidism is a common endocrine disorder caused by parathyroid 
      gland enlargement and excessive parathyroid hormone (PTH) secretion. However, the 
      precise mechanisms of tumorigenesis of the parathyroids are unknown. Here we have 
      investigated the roles of transforming growth factor (TGF)-beta and menin, the 
      product of the multiple endocrine neoplasia type 1 (Men1) gene, in the 
      proliferation and PTH production of parathyroid cells from either patients with 
      secondary hyperparathyroidism or Men1. TGF-beta was expressed in the parathyroid 
      endocrine cells. Addition of TGF-beta to parathyroid cells from patients with 
      secondary hyperparathyroidism inhibited their proliferation and PTH secretion. 
      These responses to TGF-beta were lost when menin was specifically inactivated by 
      antisense oligonucleotides. Moreover, TGF-beta did not affect the proliferation 
      and PTH production of parathyroid cells from a Men1 patient. These results 
      indicate that menin is required for TGF-beta action in the parathyroid. We 
      conclude that TGF-beta is an important autocrine/paracrine negative regulator of 
      parathyroid cell proliferation and PTH secretion and that loss of TGF-beta 
      signaling due to menin inactivation contributes to parathyroid tumorigenesis.
FAU - Sowa, Hideaki
AU  - Sowa H
AD  - Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, 
      Department of Clinical Molecular Medicine, Kobe University Graduate School of 
      Medicine, 7-5-2 Kusunoki-Cho, Chuo-ku, Kobe 650-0017, Japan.
FAU - Kaji, Hiroshi
AU  - Kaji H
FAU - Kitazawa, Riko
AU  - Kitazawa R
FAU - Kitazawa, Sohei
AU  - Kitazawa S
FAU - Tsukamoto, Tatsuo
AU  - Tsukamoto T
FAU - Yano, Shozo
AU  - Yano S
FAU - Tsukada, Toshihiko
AU  - Tsukada T
FAU - Canaff, Lucie
AU  - Canaff L
FAU - Hendy, Geoffrey N
AU  - Hendy GN
FAU - Sugimoto, Toshitsugu
AU  - Sugimoto T
FAU - Chihara, Kazuo
AU  - Chihara K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (MEN1 protein, human)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hyperparathyroidism, Secondary/*metabolism/pathology
MH  - Multiple Endocrine Neoplasia Type 1/*metabolism/pathology
MH  - Mutation
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Parathyroid Glands/metabolism/*pathology
MH  - Parathyroid Hormone/antagonists & inhibitors/*metabolism
MH  - Proto-Oncogene Proteins/*antagonists & inhibitors/genetics/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Transforming Growth Factor beta/metabolism/*pharmacology
EDAT- 2004/03/18 05:00
MHDA- 2004/04/09 05:00
CRDT- 2004/03/18 05:00
PHST- 2004/03/18 05:00 [pubmed]
PHST- 2004/04/09 05:00 [medline]
PHST- 2004/03/18 05:00 [entrez]
AID - 10.1158/0008-5472.can-03-3334 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Mar 15;64(6):2222-8. doi: 10.1158/0008-5472.can-03-3334.