Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage.
The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been identified. Wide expression of the MEN1 gene in endocrine and non-endocrine organs examined by northern blotting has been reported, but the detailed cellular distribution of the MEN1 transcript in each tissue has not yet been examined in any species. In this report, expression of the MEN1 gene in adult human tissues was studied by in situ hybridization. The MEN1 transcript was widely observed in all tissues examined, and an enhanced expression in relation to cell proliferation was seen in some organs. Cell cycle arrest at the G1-S border reduced the MEN1 mRNA level to less than 50% of that in exponentially growing asynchronous cells. The expression increased as cells entered into S phase, indicating cell cycle-associated transcriptional regulation of the MEN1 gene. Increase or decrease of the amount of menin did not affect proliferation of CHO cells under normal conditions. However, when cells were exposed to the DNA-cross-linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA synthesis. This effect was not observed when cells were exposed to ultraviolet light. These results suggest that menin may negatively regulate cell cycle under certain DNA damage.
Ikeo
Y
Y
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Sakurai
A
A
Suzuki
R
R
Zhang
M X
MX
Koizumi
S
S
Takeuchi
Y
Y
Yumita
W
W
Nakayama
J
J
Hashizume
K
K
D000328:Adult; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D006224:Cricetinae; D004249:DNA Damage; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000032:analysis / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins