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Upregulated ankyrin repeat-rich membrane spanning protein contributes to tumour progression in cutaneous melanoma.

Liao YH, Hsu SM, Yang HL, Tsai MS, Huang PH - Br. J. Cancer (2011)

Bottom Line: The immunointensity of ARMS was statistically correlated with individual clinicopathological characteristics.By RNA interference, stable melanoma cell clones with ARMS-knockdown were constructed, and were used for in vitro scratch wound, transwell invasion assays, and in vivo lung metastasis experiment.Ankyrin repeat-rich membrane spanning expression, conjunctly with tumour thickness or ulceration, may serve as a prognostic factor in patients with cutaneous melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. yihualiao@ntu.edu.tw

ABSTRACT

Background: We have previously demonstrated that overexpression of ankyrin repeat-rich membrane spanning (ARMS) protein facilitates melanoma formation via conferring apoptotic resistance. This study aims to investigate whether ARMS contributes to melanoma progression.

Method: Using immunohistochemistry, we graded the expression level of ARMS in 54 cases of primary melanoma and 46 cases of metastatic melanoma. The immunointensity of ARMS was statistically correlated with individual clinicopathological characteristics. By RNA interference, stable melanoma cell clones with ARMS-knockdown were constructed, and were used for in vitro scratch wound, transwell invasion assays, and in vivo lung metastasis experiment.

Results: Stronger immunointensity of ARMS was observed mostly in melanomas with Breslow tumour thickness >1.0  mm (Fisher's exact test, P=0.002) or with nodal metastasis (Fisher's exact test, P=0.026), and was correlated with a worse overall survival in melanoma patients (log-rank test, P=0.04). Depletion of ARMS inhibited migration, invasion, and metastatic potential of melanoma cells in vitro and in vivo. Moreover, ARMS mediated melanoma cell migration and invasion through activation of the extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signalling pathway.

Conclusion: Ankyrin repeat-rich membrane spanning expression, conjunctly with tumour thickness or ulceration, may serve as a prognostic factor in patients with cutaneous melanoma.

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Kaplan–Meier survival analysis between ARMS expression and the overall survival in melanoma patients. Patients with negative-, weak-, or moderate-ARMS expression have a significantly better overall survival than those with strong-ARMS expression (P<0.05, log-rank test).
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fig2: Kaplan–Meier survival analysis between ARMS expression and the overall survival in melanoma patients. Patients with negative-, weak-, or moderate-ARMS expression have a significantly better overall survival than those with strong-ARMS expression (P<0.05, log-rank test).

Mentions: To evaluate whether the expression of ARMS in primary cutaneous melanomas was related to patient outcome, a Kaplan–Meier survival curve was constructed. The influence of tumour thickness and ulceration, two well-recognised prognostic factors on overall survival for cutaneous melanoma (Balch et al, 2009), was also assessed in this study group as a method standard and a comparison. Our analysis showed that both Breslow thickness (log-rank test, P=0.001) and tumour ulceration (log-rank test, P=0.007) were significant prognostic factors in our patients with primary cutaneous melanoma. Importantly, a significant correlation between the immunointensity of ARMS and the patient overall survival was shown (log-rank test, P=0.04; Figure 2). Shorter median survival time in melanoma patients with stronger ARMS expression (30 months) was revealed in comparison with the patients with weak-to-moderate ARMS immunointensity (42 months). Therefore, the expression level of ARMS may serve as a molecular predictor for the prognosis of patients with primary cutaneous melanoma.


Upregulated ankyrin repeat-rich membrane spanning protein contributes to tumour progression in cutaneous melanoma.

Liao YH, Hsu SM, Yang HL, Tsai MS, Huang PH - Br. J. Cancer (2011)

Kaplan–Meier survival analysis between ARMS expression and the overall survival in melanoma patients. Patients with negative-, weak-, or moderate-ARMS expression have a significantly better overall survival than those with strong-ARMS expression (P<0.05, log-rank test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065267&req=5

fig2: Kaplan–Meier survival analysis between ARMS expression and the overall survival in melanoma patients. Patients with negative-, weak-, or moderate-ARMS expression have a significantly better overall survival than those with strong-ARMS expression (P<0.05, log-rank test).
Mentions: To evaluate whether the expression of ARMS in primary cutaneous melanomas was related to patient outcome, a Kaplan–Meier survival curve was constructed. The influence of tumour thickness and ulceration, two well-recognised prognostic factors on overall survival for cutaneous melanoma (Balch et al, 2009), was also assessed in this study group as a method standard and a comparison. Our analysis showed that both Breslow thickness (log-rank test, P=0.001) and tumour ulceration (log-rank test, P=0.007) were significant prognostic factors in our patients with primary cutaneous melanoma. Importantly, a significant correlation between the immunointensity of ARMS and the patient overall survival was shown (log-rank test, P=0.04; Figure 2). Shorter median survival time in melanoma patients with stronger ARMS expression (30 months) was revealed in comparison with the patients with weak-to-moderate ARMS immunointensity (42 months). Therefore, the expression level of ARMS may serve as a molecular predictor for the prognosis of patients with primary cutaneous melanoma.

Bottom Line: The immunointensity of ARMS was statistically correlated with individual clinicopathological characteristics.By RNA interference, stable melanoma cell clones with ARMS-knockdown were constructed, and were used for in vitro scratch wound, transwell invasion assays, and in vivo lung metastasis experiment.Ankyrin repeat-rich membrane spanning expression, conjunctly with tumour thickness or ulceration, may serve as a prognostic factor in patients with cutaneous melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. yihualiao@ntu.edu.tw

ABSTRACT

Background: We have previously demonstrated that overexpression of ankyrin repeat-rich membrane spanning (ARMS) protein facilitates melanoma formation via conferring apoptotic resistance. This study aims to investigate whether ARMS contributes to melanoma progression.

Method: Using immunohistochemistry, we graded the expression level of ARMS in 54 cases of primary melanoma and 46 cases of metastatic melanoma. The immunointensity of ARMS was statistically correlated with individual clinicopathological characteristics. By RNA interference, stable melanoma cell clones with ARMS-knockdown were constructed, and were used for in vitro scratch wound, transwell invasion assays, and in vivo lung metastasis experiment.

Results: Stronger immunointensity of ARMS was observed mostly in melanomas with Breslow tumour thickness >1.0  mm (Fisher's exact test, P=0.002) or with nodal metastasis (Fisher's exact test, P=0.026), and was correlated with a worse overall survival in melanoma patients (log-rank test, P=0.04). Depletion of ARMS inhibited migration, invasion, and metastatic potential of melanoma cells in vitro and in vivo. Moreover, ARMS mediated melanoma cell migration and invasion through activation of the extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signalling pathway.

Conclusion: Ankyrin repeat-rich membrane spanning expression, conjunctly with tumour thickness or ulceration, may serve as a prognostic factor in patients with cutaneous melanoma.

Show MeSH
Related in: MedlinePlus