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Expression of survivin and its splice variants survivin-2B and survivin-DeltaEx3 in breast cancer.

Ryan B, O'Donovan N, Browne B, O'Shea C, Crown J, Hill AD, McDermott E, O'Higgins N, Duffy MJ - Br. J. Cancer (2005)

Bottom Line: Levels of the three forms of survivin were significantly higher in the carcinomas compared to normal breast tissue (P < 0.0001).Survivin mRNA levels correlated significantly with survivin protein.Although survivin, survivin-2B and survivin-DeltaEx3 were all detected in both malignant and nonmalignant breast tissue, the predominant form was survivin.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.

ABSTRACT
Alternative splicing of survivin mRNA gives rise to multiple isoforms, that is, survivin and 3 splice variants, survivin-2B, survivin-3B and survivin-DeltaEx3. The aim of this study was to compare the expression of survivin, survivin-2B and survivin-DeltaEx3 in normal breast tissue, fibroadenomas, primary breast cancer and axillary nodal metastases. Survivin, survivin-2B and survivin-DeltaEx3 mRNA were measured using semiquantitative RT-PCR. In the primary carcinomas, we related mRNA for each form of survivin to both survivin protein and apoptosis. For each type of breast tissue, survivin was the predominant form detected, being present in 146 out of 156 (93.6%) primary breast carcinomas, 11 out of 11 (100%) axillary nodal metastases, 21 out of 31 (67.7%) fibroadenomas and five out of 22 (22.7%) specimens of normal breast tissue. Levels of the three forms of survivin were significantly higher in the carcinomas compared to normal breast tissue (P < 0.0001). Levels of both survivin-2B and survivin-DeltaEx3 but not survivin were significantly higher in nodal metastases than primary carcinomas. Survivin mRNA levels correlated significantly with survivin protein. Finally, both survivin and survivin-DeltaEx3 but not survivin-2B correlated positively with apoptosis. Although survivin, survivin-2B and survivin-DeltaEx3 were all detected in both malignant and nonmalignant breast tissue, the predominant form was survivin. Our results suggest that the different forms of survivin may have different roles in apoptosis in breast cancer.

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Related in: MedlinePlus

Relationship between both survivin mRNA (A) and survivin-ΔEx3 mRNA (B) and apoptosis levels in primary breast cancer. OD units are optical density units.
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fig2: Relationship between both survivin mRNA (A) and survivin-ΔEx3 mRNA (B) and apoptosis levels in primary breast cancer. OD units are optical density units.

Mentions: Survivin has been shown to inhibit apoptosis but the relationship between the survivin splice variants and apoptosis has not previously been investigated in breast cancer. Levels of apoptosis were measured in 65 of the primary carcinoma samples using the Cell Death Detection ELISA, which measures nucleosomes released during DNA fragmentation. As shown in Figures 2A and B, levels of both survivin and survivin-ΔEx3 mRNA showed a moderate positive correlation with apoptosis (for survivin, r=0.38, P=0.012; for survivin-ΔEx3, r=0.37, P=0.023). In contrast, no significant correlation was found between survivin-2B and apoptosis (n=65, r=0.28, P=0.121).


Expression of survivin and its splice variants survivin-2B and survivin-DeltaEx3 in breast cancer.

Ryan B, O'Donovan N, Browne B, O'Shea C, Crown J, Hill AD, McDermott E, O'Higgins N, Duffy MJ - Br. J. Cancer (2005)

Relationship between both survivin mRNA (A) and survivin-ΔEx3 mRNA (B) and apoptosis levels in primary breast cancer. OD units are optical density units.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361728&req=5

fig2: Relationship between both survivin mRNA (A) and survivin-ΔEx3 mRNA (B) and apoptosis levels in primary breast cancer. OD units are optical density units.
Mentions: Survivin has been shown to inhibit apoptosis but the relationship between the survivin splice variants and apoptosis has not previously been investigated in breast cancer. Levels of apoptosis were measured in 65 of the primary carcinoma samples using the Cell Death Detection ELISA, which measures nucleosomes released during DNA fragmentation. As shown in Figures 2A and B, levels of both survivin and survivin-ΔEx3 mRNA showed a moderate positive correlation with apoptosis (for survivin, r=0.38, P=0.012; for survivin-ΔEx3, r=0.37, P=0.023). In contrast, no significant correlation was found between survivin-2B and apoptosis (n=65, r=0.28, P=0.121).

Bottom Line: Levels of the three forms of survivin were significantly higher in the carcinomas compared to normal breast tissue (P < 0.0001).Survivin mRNA levels correlated significantly with survivin protein.Although survivin, survivin-2B and survivin-DeltaEx3 were all detected in both malignant and nonmalignant breast tissue, the predominant form was survivin.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.

ABSTRACT
Alternative splicing of survivin mRNA gives rise to multiple isoforms, that is, survivin and 3 splice variants, survivin-2B, survivin-3B and survivin-DeltaEx3. The aim of this study was to compare the expression of survivin, survivin-2B and survivin-DeltaEx3 in normal breast tissue, fibroadenomas, primary breast cancer and axillary nodal metastases. Survivin, survivin-2B and survivin-DeltaEx3 mRNA were measured using semiquantitative RT-PCR. In the primary carcinomas, we related mRNA for each form of survivin to both survivin protein and apoptosis. For each type of breast tissue, survivin was the predominant form detected, being present in 146 out of 156 (93.6%) primary breast carcinomas, 11 out of 11 (100%) axillary nodal metastases, 21 out of 31 (67.7%) fibroadenomas and five out of 22 (22.7%) specimens of normal breast tissue. Levels of the three forms of survivin were significantly higher in the carcinomas compared to normal breast tissue (P < 0.0001). Levels of both survivin-2B and survivin-DeltaEx3 but not survivin were significantly higher in nodal metastases than primary carcinomas. Survivin mRNA levels correlated significantly with survivin protein. Finally, both survivin and survivin-DeltaEx3 but not survivin-2B correlated positively with apoptosis. Although survivin, survivin-2B and survivin-DeltaEx3 were all detected in both malignant and nonmalignant breast tissue, the predominant form was survivin. Our results suggest that the different forms of survivin may have different roles in apoptosis in breast cancer.

Show MeSH
Related in: MedlinePlus