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BRAFV600E mutations in malignant melanoma are associated with increased expressions of BAALC.

Schrama D, Keller G, Houben R, Ziegler CG, Vetter-Kauczok CS, Ugurel S, Becker JC - J Carcinog (2008)

Bottom Line: This analysis revealed a more than two fold down-regulation of 43 and an increase of 39 gene products.BAALC (Brain and acute Leukaemia, cytoplasmatic) was most prominently regulated, since it was up-regulated in mutated cell lines by a mean of 11.45.BAALC, which has been associated with cell dedifferentiation and migration, may function as a downstream effector of activating BRAF mutations during melanomagenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Dermatology, Julius-Maximilians University, Würzburg, Germany. schrama_d@klinik.uni-wuerzburg.de.

ABSTRACT

Unlabelled: BACHGROUND: Activating BRAF mutations are present in approximately 50% of melanomas. Although different downstream target genes of the most common mutant V600E have been identified, the contribution of activating BRAF mutations to malignant transformation needs further clarification.

Methods: Microarray gene analysis was performed for human melanoma cell lines harboring BRAFV600E mutations in comparison to cell lines without this mutation.

Results: This analysis revealed a more than two fold down-regulation of 43 and an increase of 39 gene products. BAALC (Brain and acute Leukaemia, cytoplasmatic) was most prominently regulated, since it was up-regulated in mutated cell lines by a mean of 11.45. Real time PCR analyses with RNA from melanoma cell lines (n = 30) confirmed the BRAF-activation dependent up-regulation of BAALC.

Conclusion: BAALC, which has been associated with cell dedifferentiation and migration, may function as a downstream effector of activating BRAF mutations during melanomagenesis.

No MeSH data available.


Related in: MedlinePlus

Relative mRNA expression of BAALC (brain and acute leukaemia, cytoplasmatic) in human malignant melanoma cell lines as revealed by real time PCR. 16 melanoma cell lines harboring BRAF mutation were compared to 9 cell lines with RAS mutation and 5 without any mutation in these genes. (* p < 0.01). As calibrator served a wild type melanoma cell line.
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Figure 1: Relative mRNA expression of BAALC (brain and acute leukaemia, cytoplasmatic) in human malignant melanoma cell lines as revealed by real time PCR. 16 melanoma cell lines harboring BRAF mutation were compared to 9 cell lines with RAS mutation and 5 without any mutation in these genes. (* p < 0.01). As calibrator served a wild type melanoma cell line.

Mentions: The distinct increase of BAALC expression in all three BRAFV600E mutated melanoma cell lines suggests a possible function of BAALC associated with activated BRAF mutations in melanoma and mediating cell dedifferentiation and motility. As mentioned before, complementary experiments using real time PCR analyses to measure the relative mRNA expression of BAALC have to be performed to confirm this correlation. To this end, BAALC expression was determined in 16 cell lines mutated for BRAF, 5 wild type BRAF melanoma cell lines as well as 9 melanoma cell lines in which the MAP kinase pathway was activated by RAS mutations. These analyses validated the first observations; BRAFV600E cell lines showed significantly (p < 0.01) elevated mRNA levels of BAALC (Fig. 1a) when compared to wild type cell lines. Notably, over-expression of BAALC was also significant when compared to RAS mutated cell lines (Fig. 1a). Importantly, most of the cell lines analyzed were short term cultures which should therefore resemble closely the parental tumor (table 1). Our results are in accordance with previous published data demonstrating that only a portion of regulated genes in cell lines with BRAF or NRAS mutations are common among the different mutations [10,11]. The different expression patterns might be ascribed to the differential capacity to receive input signals and to pass these on to various effectors.


BRAFV600E mutations in malignant melanoma are associated with increased expressions of BAALC.

Schrama D, Keller G, Houben R, Ziegler CG, Vetter-Kauczok CS, Ugurel S, Becker JC - J Carcinog (2008)

Relative mRNA expression of BAALC (brain and acute leukaemia, cytoplasmatic) in human malignant melanoma cell lines as revealed by real time PCR. 16 melanoma cell lines harboring BRAF mutation were compared to 9 cell lines with RAS mutation and 5 without any mutation in these genes. (* p < 0.01). As calibrator served a wild type melanoma cell line.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2483271&req=5

Figure 1: Relative mRNA expression of BAALC (brain and acute leukaemia, cytoplasmatic) in human malignant melanoma cell lines as revealed by real time PCR. 16 melanoma cell lines harboring BRAF mutation were compared to 9 cell lines with RAS mutation and 5 without any mutation in these genes. (* p < 0.01). As calibrator served a wild type melanoma cell line.
Mentions: The distinct increase of BAALC expression in all three BRAFV600E mutated melanoma cell lines suggests a possible function of BAALC associated with activated BRAF mutations in melanoma and mediating cell dedifferentiation and motility. As mentioned before, complementary experiments using real time PCR analyses to measure the relative mRNA expression of BAALC have to be performed to confirm this correlation. To this end, BAALC expression was determined in 16 cell lines mutated for BRAF, 5 wild type BRAF melanoma cell lines as well as 9 melanoma cell lines in which the MAP kinase pathway was activated by RAS mutations. These analyses validated the first observations; BRAFV600E cell lines showed significantly (p < 0.01) elevated mRNA levels of BAALC (Fig. 1a) when compared to wild type cell lines. Notably, over-expression of BAALC was also significant when compared to RAS mutated cell lines (Fig. 1a). Importantly, most of the cell lines analyzed were short term cultures which should therefore resemble closely the parental tumor (table 1). Our results are in accordance with previous published data demonstrating that only a portion of regulated genes in cell lines with BRAF or NRAS mutations are common among the different mutations [10,11]. The different expression patterns might be ascribed to the differential capacity to receive input signals and to pass these on to various effectors.

Bottom Line: This analysis revealed a more than two fold down-regulation of 43 and an increase of 39 gene products.BAALC (Brain and acute Leukaemia, cytoplasmatic) was most prominently regulated, since it was up-regulated in mutated cell lines by a mean of 11.45.BAALC, which has been associated with cell dedifferentiation and migration, may function as a downstream effector of activating BRAF mutations during melanomagenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Dermatology, Julius-Maximilians University, Würzburg, Germany. schrama_d@klinik.uni-wuerzburg.de.

ABSTRACT

Unlabelled: BACHGROUND: Activating BRAF mutations are present in approximately 50% of melanomas. Although different downstream target genes of the most common mutant V600E have been identified, the contribution of activating BRAF mutations to malignant transformation needs further clarification.

Methods: Microarray gene analysis was performed for human melanoma cell lines harboring BRAFV600E mutations in comparison to cell lines without this mutation.

Results: This analysis revealed a more than two fold down-regulation of 43 and an increase of 39 gene products. BAALC (Brain and acute Leukaemia, cytoplasmatic) was most prominently regulated, since it was up-regulated in mutated cell lines by a mean of 11.45. Real time PCR analyses with RNA from melanoma cell lines (n = 30) confirmed the BRAF-activation dependent up-regulation of BAALC.

Conclusion: BAALC, which has been associated with cell dedifferentiation and migration, may function as a downstream effector of activating BRAF mutations during melanomagenesis.

No MeSH data available.


Related in: MedlinePlus