GPRC5A:  A potential tumor suppressor and oncogene

Acquafreda, Thais; Soprano, Kenneth J.; Soprano, Dianne Robert

doi:10.4161/cbt.8.10.8417

Cited by 11 publications

(8 citation statements)

References 13 publications

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“…Recently, miR-103a-3p was shown to control the expression of GPRC5A mRNA and its protein product in pancreatic cells [25] . GPRC5A acts as oncogene or tumor suppressor in different types of cancer [26] but nothing is known about GPRC5A in mesothelioma. Thus, it might be reasonable to evaluate the potential roles of miR-103a-3p and GPRC5A in mesothelioma.…”

Section: Discussionmentioning

confidence: 99%

Combination of MiR-103a-3p and Mesothelin Improves the Biomarker Performance of Malignant Mesothelioma Diagnosis

et al. 2014

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BackgroundFor the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low sensitivity. It might be reasonable to combine biomarkers of different molecular classes in order to improve the overall performance. The aim of this study was to assess the performance of the combination of mesothelin and miR-103a-3p as blood-based biomarker for mesothelioma.Methods/Principal FindingsMesothelin concentration in plasma and miR-103a-3p levels in the cellular blood fraction were analyzed in 43 male mesothelioma patients and 52 male controls formerly exposed to asbestos. For the discrimination of epithelioid and biphasic mesothelioma from asbestos-exposed controls mesothelin and miR-103a-3p showed 74% and 89% sensitivity and 85% and 63% specificity, respectively. For the combination of mesothelin and miR-103a-3p a sensitivity of 95% and a specificity of 81% were calculated.Conclusions/SignificanceThe results of this study show that the combination of mesothelin and miR-103a-3p improves the diagnostic performance of individual blood-based biomarker to detect malignant mesothelioma. The obtained results indicate that the use of biomarkers of different molecular classes might be a reasonable approach to assemble a biomarker panel.

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Section: Discussionmentioning

confidence: 99%

Combination of MiR-103a-3p and Mesothelin Improves the Biomarker Performance of Malignant Mesothelioma Diagnosis

et al. 2014

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“…Interestingly, the gene whose transcription is the most differentially regulated by the feeder layer (Retinoic acid receptor responder protein 3 (RARRES3/ TIG3 ): 21-fold repression) turned out also to be a well known retinoic acid inducible tumor suppressor gene [41], a gene also involved in growth regulation and epithelial differentiation [42,43]. Similarly, the protein product encoded by GPRC5A, another retinoic acid responding gene whose expression is heavily downregulated by the feeder layer (see Figure 6 and Table S1), was also reported to function as a potential tumor suppressor gene [44,45]. Consistent with the improved properties of keratinocytes grown with a feeder layer, suppression of PRC5A expression in PRC5A(−/−) knockout mice is also associated with increased epithelial lung cell proliferation, resistance to cell death in suspension, and increased basal, tumor necrosis factor alpha-induced, and lipopolysaccharide-induced NF-kappaB activation [46].…”

Section: Discussionmentioning

confidence: 99%

Irradiated Human Dermal Fibroblasts Are as Efficient as Mouse Fibroblasts as a Feeder Layer to Improve Human Epidermal Cell Culture Lifespan

Bisson

Rochefort

Lavoie

et al. 2013

IJMS

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A fibroblast feeder layer is currently the best option for large scale expansion of autologous skin keratinocytes that are to be used for the treatment of severely burned patients. In a clinical context, using a human rather than a mouse feeder layer is desirable to reduce the risk of introducing animal antigens and unknown viruses. This study was designed to evaluate if irradiated human fibroblasts can be used in keratinocyte cultures without affecting their morphological and physiological properties. Keratinocytes were grown either with or without a feeder layer in serum-containing medium. Our results showed that keratinocytes grown either on an irradiated human feeder layer or irradiated 3T3 cells (i3T3) can be cultured for a comparable number of passages. The average epithelial cell size and morphology were also similar. On the other hand, keratinocytes grown without a feeder layer showed heavily bloated cells at early passages and stop proliferating after only a few passages. On the molecular aspect, the expression level of the transcription factor Sp1, a useful marker of keratinocytes lifespan, was maintained and stabilized for a high number of passages in keratinocytes grown with feeder layers whereas Sp1 expression dropped quickly without a feeder layer. Furthermore, gene profiling on microarrays identified potential target genes whose expression is differentially regulated in the absence or presence of an i3T3 feeder layer and which may contribute at preserving the growth characteristics of these cells. Irradiated human dermal fibroblasts therefore provide a good human feeder layer for an effective expansion of keratinocytes in vitro that are to be used for clinical purposes.

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“…this locus is within suspected tumor-suppressor gene GPRC5A (Tao et al 2007;Acquafreda et al 2009), suggesting the possibility that persistent STAT3 activation due to mutation of GPRC5A ) may be a contributing factor in these patients. Interestingly, both samples 10-822 [carrying the t(17;19)] and 10-838 were from relapsed patients who eventually died of their disease, suggesting that GPRC5A disruption should be investigated for potential prognostic significance.…”

Section: Deregulation Of Replication Domains In Leukemiamentioning

confidence: 98%

Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia

et al. 2012

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Abnormal replication timing has been observed in cancer but no study has comprehensively evaluated this misregulation. We generated genome-wide replication-timing profiles for pediatric leukemias from 17 patients and three cell lines, as well as normal B and T cells. Nonleukemic EBV-transformed lymphoblastoid cell lines displayed highly stable replicationtiming profiles that were more similar to normal T cells than to leukemias. Leukemias were more similar to each other than to B and T cells but were considerably more heterogeneous than nonleukemic controls. Some differences were patient specific, while others were found in all leukemic samples, potentially representing early epigenetic events. Differences encompassed large segments of chromosomes and included genes implicated in other types of cancer. Remarkably, differences that distinguished leukemias aligned in register to the boundaries of developmentally regulated replicationtiming domains that distinguish normal cell types. Most changes did not coincide with copy-number variation or translocations. However, many of the changes that were associated with translocations in some leukemias were also shared between all leukemic samples independent of the genetic lesion, suggesting that they precede and possibly predispose chromosomes to the translocation. Altogether, our results identify sites of abnormal developmental control of DNA replication in cancer that reveal the significance of replication-timing boundaries to chromosome structure and function and support the replication domain model of replication-timing regulation. They also open new avenues of investigation into the chromosomal basis of cancer and provide a potential novel source of epigenetic cancer biomarkers.

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GPRC5A: A potential tumor suppressor and oncogene

Cited by 11 publications

References 13 publications

Combination of MiR-103a-3p and Mesothelin Improves the Biomarker Performance of Malignant Mesothelioma Diagnosis

Combination of MiR-103a-3p and Mesothelin Improves the Biomarker Performance of Malignant Mesothelioma Diagnosis

Irradiated Human Dermal Fibroblasts Are as Efficient as Mouse Fibroblasts as a Feeder Layer to Improve Human Epidermal Cell Culture Lifespan

Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia

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