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Evidence for a tumour suppressive function of APRG1 in breast cancer.
Breast Cancer Res Treat. 2005 Sep; 93(2):97-100.BC

Abstract

INTRODUCTION

Deletion mapping studies have shown that genes in the region 3p21.3 are often deleted in epithelial malignancies. Although the regions deleted differ between individual cancers there appears to be a specificity for the type of malignancy produced. As a result this area of chromosome 3 is thought to contain multiple tumour suppressor genes. The present study concentrates on one gene in that region, APRG1. This gene codes for a protein, which has been implicated in cell membrane interactions. The aim was to determine using quantitative PCR whether the levels of this gene were negatively correlated with clinical outcome in breast cancer.

METHODS

One hundred and twenty tumour tissues and 33 normal tissues were analyzed. Levels of transcription of APRG1 were determined using real-time quantitative PCR. APRG1 expression was normalized against CK19. Levels of expression were analyzed against staging, nodal involvement, grade, distant metastasis and survival over a 6 year follow up period.

RESULTS

Levels of APRG1 mRNA were lower in malignant tissues. They fell further with increasing stage using the TNM classification This became statistically significant when TNM stages 3 and 4 were compared to TNM 1 (p = 0.0046, p = 0.04, t-test). They were lower in those with positive nodes although this did not reach statistical significance. There was a statistically significant reduction in APRG1 in grade 3 tumours cf. grade 1 (p = 0.0081). APRG1 expression was highly negatively correlated with progressive disease: alive with metastasis (p = 0.0069), local recurrence (p = 0.0055), died of breast cancer (p = 0.11), all progressive disease (p = 0.035).

CONCLUSION

This study shows a compelling trend for APRG1 transcription levels to be lower in malignant tissues and lower still in those patients who develop progressive disease. There was also a statistically significant difference in APRG1 levels between grade 3 and grade 1 tumours. These results are highly suggestive of APRG1 acting as a tumour suppressor gene.

Authors+Show Affiliations

St George's Hospital, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16187228

Citation

Leris, A C A., et al. "Evidence for a Tumour Suppressive Function of APRG1 in Breast Cancer." Breast Cancer Research and Treatment, vol. 93, no. 2, 2005, pp. 97-100.
Leris AC, Roberts TR, Jiang WG, et al. Evidence for a tumour suppressive function of APRG1 in breast cancer. Breast Cancer Res Treat. 2005;93(2):97-100.
Leris, A. C., Roberts, T. R., Jiang, W. G., Newbold, R. F., & Mokbel, K. (2005). Evidence for a tumour suppressive function of APRG1 in breast cancer. Breast Cancer Research and Treatment, 93(2), 97-100.
Leris AC, et al. Evidence for a Tumour Suppressive Function of APRG1 in Breast Cancer. Breast Cancer Res Treat. 2005;93(2):97-100. PubMed PMID: 16187228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for a tumour suppressive function of APRG1 in breast cancer. AU - Leris,A C A, AU - Roberts,T R, AU - Jiang,W G, AU - Newbold,R F, AU - Mokbel,K, PY - 2005/9/28/pubmed PY - 2006/1/27/medline PY - 2005/9/28/entrez SP - 97 EP - 100 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 93 IS - 2 N2 - INTRODUCTION: Deletion mapping studies have shown that genes in the region 3p21.3 are often deleted in epithelial malignancies. Although the regions deleted differ between individual cancers there appears to be a specificity for the type of malignancy produced. As a result this area of chromosome 3 is thought to contain multiple tumour suppressor genes. The present study concentrates on one gene in that region, APRG1. This gene codes for a protein, which has been implicated in cell membrane interactions. The aim was to determine using quantitative PCR whether the levels of this gene were negatively correlated with clinical outcome in breast cancer. METHODS: One hundred and twenty tumour tissues and 33 normal tissues were analyzed. Levels of transcription of APRG1 were determined using real-time quantitative PCR. APRG1 expression was normalized against CK19. Levels of expression were analyzed against staging, nodal involvement, grade, distant metastasis and survival over a 6 year follow up period. RESULTS: Levels of APRG1 mRNA were lower in malignant tissues. They fell further with increasing stage using the TNM classification This became statistically significant when TNM stages 3 and 4 were compared to TNM 1 (p = 0.0046, p = 0.04, t-test). They were lower in those with positive nodes although this did not reach statistical significance. There was a statistically significant reduction in APRG1 in grade 3 tumours cf. grade 1 (p = 0.0081). APRG1 expression was highly negatively correlated with progressive disease: alive with metastasis (p = 0.0069), local recurrence (p = 0.0055), died of breast cancer (p = 0.11), all progressive disease (p = 0.035). CONCLUSION: This study shows a compelling trend for APRG1 transcription levels to be lower in malignant tissues and lower still in those patients who develop progressive disease. There was also a statistically significant difference in APRG1 levels between grade 3 and grade 1 tumours. These results are highly suggestive of APRG1 acting as a tumour suppressor gene. SN - 0167-6806 UR - https://www.unboundmedicine.com/medline/citation/16187228/Evidence_for_a_tumour_suppressive_function_of_APRG1_in_breast_cancer_ L2 - https://doi.org/10.1007/s10549-005-4169-z DB - PRIME DP - Unbound Medicine ER -