FLRG (follistatin-related gene), a new target of chromosomal rearrangement in malignant blood disorders

Hayette, Sandrine; Gadoux, Mylène; Martel, Sylvie; Bertrand, S.; Tigaud, Isabelle; Magaud, Jean‐Pierre; Rimokh, Ruth

doi:10.1038/sj.onc.1201807

Cited by 109 publications

(114 citation statements)

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“…One chromosome marker add(19)(p13) was common to both cell lines. Some hypoxia-associated genes, including follistatin like 3 (FSTL3), CA9, mitogen-activated protein kinase organizer 1 (MORG1), and angiopoietin-like 4 (ANGPTL4), are located near 9p13 (Hayette et al, 1998;Biron-Shental et al, 2008). The upregulation of FSTL3 mRNA has previously been observed as a response to hypoxia in human trophoblasts, thus suggesting a role for HIF1-a (Biron-Shental et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Establishment and characterization of a new hypoxia-resistant cancer cell line, OCUM-12/Hypo, derived from a scirrhous gastric carcinoma

et al. 2010

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BACKGROUND: Many kinds of solid tumour have heterogeneously a hypoxic environment. Tumour hypoxia reported to be associated with more aggressive tumour phenotypes such as high metastatic ability and resistance to various anti-cancer therapies which may lead to a poorer prognosis. However, the mechanisms by which hypoxia affects the aggressive phenotypes remain unclear. METHODS: We established a scirrhous gastric carcinoma cell line (OCUM-12) from ascites associated with scirrhous gastric carcinoma, and a hypoxia-resistant cancer cell line (OCUM-12/Hypo) was cloned from OCUM-12 cells by continuous exposure to 1% oxygen. RESULTS: Histologic findings from orthotopic tumours derived from parent OCUM-12 cells and daughter OCUM-12/Hypo cells revealed poorly differentiated adenocarcinoma with extensive fibrosis that resembled human scirrhous gastric cancer. Necrotic lesions were frequently detected in the OCUM-12 tumours but were rarely found in the OCUM-12/Hypo tumours, although both types had multiple hypoxic loci. Apoptosis rate of OCUM-12 cells was increased to 24.7% at 1% O 2 , whereas that of OCUM-12/ Hypo was 5.6%. The OCUM-12/Hypo orthotopic models developed multiple metastases to the peritoneum and lymph nodes, but the OCUM-12 models did not. OCUM-12/Hypo cells showed epithelial-to-mesenchymal transition and high migratory and invasive activities in comparison with OCUM-12 cells. The mRNA expression levels of both E-cadherin and zonula occludens ZO-1 and ZO-2 decreased in OCUM-12/Hypo cells, and that of vimentin, Snail-1, Slug/Snail-2, Twist, ZEB-1, ZEB-2, matrix metalloproteinase-1 (MMP-1), and MMP-2 were increased in OCUM-12/Hypo cells. CONCLUSION: OCUM-12 and OCUM-12/Hypo may be useful for the elucidation of disease progression associated with scirrhous gastric cancer in the setting of chronic hypoxia.

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Section: Discussionmentioning

confidence: 99%

Establishment and characterization of a new hypoxia-resistant cancer cell line, OCUM-12/Hypo, derived from a scirrhous gastric carcinoma

et al. 2010

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“…Recently, a new protein that shares the characteristic 10-cysteine structures of follistatin domains was cloned from a B cell leukemia line based on its overexpression in response to a chromosomal translocation (10). Referred to as follistatin-related gene (FLRG) on the basis of the striking sequence homology with follistatin (11), it also shares a similar Nterminal domain with follistatin, a region that is crucial for the binding to activin (12) and, like follistatin, it binds strongly to activin (11,13,14).…”

Section: Introductionmentioning

confidence: 99%

Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma

Ciarmela

Florio²,

Sigurðardóttir³

et al. 2004

European Journal of Endocrinology

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P Ciarmela and P Florio contributed equally to this work AbstractObjective: Activin A is a multifunctional growth and cell differentiation factor produced by normal endometrium, and secreted in high amounts by endometrial adenocarcinoma. In the present study we evaluated the expression of two inhibitory activin A ligands, follistatin and follistatin-related gene (FLRG), in endometrial adenocarcinoma and in age-matched healthy human endometrium. Design and methods: Atropic menopausal (n ¼ 13) and tumoral (n ¼ 9 adenocarcinoma) tissues were processed to evaluate mRNA expression levels (by semiquantitative RT-PCR) and peptide localization (by immunohistochemistry). Differences were evaluated by the unpaired t-test and assumed to be statistically significant when P , 0.05. Results: Both control and tumoral endometrial samples express and localize follistatin and FLRG. However, whereas follistatin mRNA expression did not differ significantly, FLRG was significantly lower in endometrial adenocarcinoma than in healthy endometrial specimens (P , 0.0001). With respect to the localization of proteins, follistatin was immunolocalized in endometrial epithelial and vascular cells both in tumoral and healthy endometrium without any significant difference in intensity. Nuclear and cytoplasmic FLRG immunolocalization was seen in glands, and only nuclear immunolocalization was found in stroma and vessels of healthy endometrium. FLRG was weakly immunostained in endometrial adenocarcinoma. Conclusions: Whilst follistatin expression is unchanged, FLRG is down-regulated in endometrial carcinoma. As activin A is a differentiation factor of human endometrium, the present findings support an imbalance between increased activin A and decreased FLRG expression in endometrial cancer, so that the failure of the activin A pathway through FLRG may be pivotal in endometrial tumorigenesis.

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“…In addition to follistatin and FRP, other FS domain-bearing proteins, such as secreted protein, acidic and rich in cysteine (SPARC), SC1/hevin, testican, QR1, and follistatin-related gene protein (FLRG), have been cloned, and together, they compose the follistatin family (11). FLRG is a translated product of follistatinrelated gene (FLRG), which was isolated from a B cell leukemia cell line (12). FRP and FLRG are different proteins (12,13) and are listed in the OMIM database under the names follistatin-like 1 (FSTL1) and follistatin-like 3 (FSTL3), respectively (13,14).…”

mentioning

confidence: 99%

“…FLRG is a translated product of follistatinrelated gene (FLRG), which was isolated from a B cell leukemia cell line (12). FRP and FLRG are different proteins (12,13) and are listed in the OMIM database under the names follistatin-like 1 (FSTL1) and follistatin-like 3 (FSTL3), respectively (13,14). Follistatin and FLRG have activin-binding activity and inhibit activin-mediated gene transcription (15).…”

mentioning

confidence: 99%

Ameliorative effects of follistatin‐related protein/TSC‐36/FSTL1 on joint inflammation in a mouse model of arthritis

Kawabata¹,

Tanaka²,

Fujii³

et al. 2004

Arthritis & Rheumatism

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FLRG (follistatin-related gene), a new target of chromosomal rearrangement in malignant blood disorders

Cited by 109 publications

References 10 publications

Establishment and characterization of a new hypoxia-resistant cancer cell line, OCUM-12/Hypo, derived from a scirrhous gastric carcinoma

Establishment and characterization of a new hypoxia-resistant cancer cell line, OCUM-12/Hypo, derived from a scirrhous gastric carcinoma

Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma

Ameliorative effects of follistatin‐related protein/TSC‐36/FSTL1 on joint inflammation in a mouse model of arthritis

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