Disease relevance of Mn1

• Mn1 null mice, however, were found to die at birth or shortly thereafter as the result of a cleft palate [1].
• MN1 was highly expressed in some patients with acute lymphoblastic but not chronic lymphocytic or myeloid leukemia [2].
• These include SW-527 and SW-613 mammary carcinomas, SW-598 meningioma, SW-608 astrocytoma, SW-732 cervix carcinoma, and SW-733 bladder carcinoma [3].
• To evaluate S6K as a candidate meningioma progression gene, we generated IOMM-Lee human meningioma cell lines overexpressing S6K [4].
• Biallelic mutations in the neurofibromatosis 2 (NF2) gene are linked to schwannoma and meningioma tumorigenesis [5].

High impact information on Mn1

• We show that, beginning at four months of age, thirty percent of mice with arachnoidal cell Cre-mediated excision of Nf2 exon 2 developed a range of meningioma subtypes histologically similar to the human tumors [6].
• Meningioma, a tumor of the meninges covering the central nervous system, shows frequent loss of material from human chromosome 22 [7].
• Mouse antisera specific for desmosomal adhesion molecules of suprabasal skin cells, meninges, and meningioma [8].
• In conclusion, our data suggest MN1 overexpression as a new prognostic marker in AML with normal cytogenetics [2].
• Targeted disruption of the Mn1 oncogene results in severe defects in development of membranous bones of the cranial skeleton [1].

Chemical compound and disease context of Mn1

• Currently, mifepristone is being tested in clinical trials on meningioma and breast cancer [9].
• Hydroxyurea for treatment of unresectable and recurrent meningiomas. I. Inhibition of primary human meningioma cells in culture and in meningioma transplants by induction of the apoptotic pathway [10].
• Consequently, the disruptions due to merlin inactivation in the progression of malignant mesothelioma may represent a tumor suppressor role operating by a different pathway than that in schwannoma or meningioma [11].

Biological context of Mn1

• Four pseudogenes including those for small protein G, laminin receptor, human transposase protein and meningioma-expressed antigen were identified [12].
• We have developed a meningioma cell line by retrovirally transducing primary cells derived from a human WHO grade I meningothelial meningioma with the human telomerase reverse transcriptase (hTERT) gene, which enables bypassing cellular senescence [13].
• Short-term treatment of meningioma cell cultures with hydroxyurea for 24 to 48 hours resulted in discrete oligonucleosomal fragments (DNA ladder), another characteristic sign of apoptosis [10].
• Rearrangement of the sis gene was found in one meningioma [14].
• These data provide evidence that hydroxyurea is a powerful inhibitor of meningioma cell growth, most likely by causing apoptosis in the tumor cells [10].

Anatomical context of Mn1

• mac25, a retinoic acid-inducible gene that is expressed at high levels in senescent epithelial cells, was initially cloned as a gene that is differentially expressed in meningioma [15].
• One clone, designated Ben-Men-1, was characterized in more detail, and exhibited typical cytological, immunocytochemical, ultrastructural and genetical features of meningioma, including whorl formation, expression of epithelial membrane antigen, desmosomes and interdigitating cell processes, as well as -22q [13].
• In a man with a large sphenoid wing meningioma invading the right cavernous sinus and the temporal base, the intracranial tumor mass was reduced by 60% during 6 months of treatment [16].
• The fourth patient with the malignant meningioma in the left cerebellopontine angle has had no recurrence for 24 months [16].
• Cells (10(6)/10 microl) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal white matter or subdural space of athymic mice [17].

Associations of Mn1 with chemical compounds

• Long-term treatment with hydroxyurea may result in full remission of tumors in meningioma patients [16].
• Effect of the antiprogesterone RU-38486 on meningioma implanted into nude mice [18].
• CONCLUSIONS.: Celecoxib inhibits meningioma growth in vivo at plasma levels achievable in humans [19].
• RESULTS: The addition of diltiazem or verapamil to HU or RU486 augmented meningioma growth inhibition by 20 to 60% in vitro [20].
• METHODS: Primary and malignant (IOMM-Lee) meningioma cell lines were treated with HU, RU486, or either of these plus diltiazem or verapamil [20].

Other interactions of Mn1

• OBJECT: The authors have previously demonstrated that modulation of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis can significantly affect meningioma growth in vitro [21].
• The antibody specifically reacted with medulloblastomas, supratentorial primitive neuroectodermal tumours (SPNETs) and gliomas, but not with other neuroectodermally derived tumours (neuroblastoma and melanoma) or with other kinds of tumours (meningioma, neurinoma, leukaemia, and small cell lung cancer) [22].
• A3 reacted specifically with MT-8 cells, with another rat MFH-derived cell line (MT-9) and with their induced tumours in syngeneic rats, but not with other rat tumours such as fibrosarcoma, histiocytic sarcoma, malignant meningioma, uterine leiomyosarcoma, endometrial stromal sarcoma, mononuclear cell leukaemia and malignant schwannoma [23].

Analytical, diagnostic and therapeutic context of Mn1

• We quantified MN1 expression by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 142 adult patients with AML with normal cytogenetics treated uniformly in trial AML-SHG 01/99 [2].
• Following subdural transplantation into nude mice, tumor tissue with typical histological features of meningothelial meningioma was found [13].
• Tumor take and growth of xenograft meningioma cells in an in vivo model have previously been only partially successful [24].
• Only three of those implanted from cell cultures were similar to the original tumor; the other three displayed features characteristic of malignant meningioma [25].
• A woman with a large ball-shaped meningioma of the right sphenoid wing invading the cavernous sinus exhibited a 74% decrease of the initial tumor volume in 10 months of treatment with oral hydroxyurea [16].

References