Limits...
Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer.

Campbell EJ, McDuff E, Tatarov O, Tovey S, Brunton V, Cooke TG, Edwards J - Br. J. Cancer (2008)

Bottom Line: High level of nuclear activated Src was significantly associated with improved overall survival (P=0.047) and lower recurrence rates on tamoxifen (P=0.02).Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (P<0.05).On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (P=0.004).

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Sciences and Molecular Pathology, Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.

ABSTRACT
Elevated c-Src protein expression has been shown in breast cancer and in vitro evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan-Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (P=0.047) and lower recurrence rates on tamoxifen (P=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (P<0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (P=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in de novo endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome.

Show MeSH

Related in: MedlinePlus

The different localisation of activated c-Src, SrcpY416 in prostate and breast tumour samples are shown. In breast tumours, activated c-Src was most commonly present in the cell cytoplasm and the cell nucleus (A and B). In the prostate cancer (C and D), the majority of staining observed for phosphorylated c-Src was located to the membrane, and nuclear expression was rarely observed.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2600702&req=5

fig2: The different localisation of activated c-Src, SrcpY416 in prostate and breast tumour samples are shown. In breast tumours, activated c-Src was most commonly present in the cell cytoplasm and the cell nucleus (A and B). In the prostate cancer (C and D), the majority of staining observed for phosphorylated c-Src was located to the membrane, and nuclear expression was rarely observed.

Mentions: A total of 262 ER-positive tumour samples were analysed for activated c-Src expression. 57.3% (150 out of 262) of tumours expressed activated Src in the cytoplasm; median histoscore 20 (interquartile range 0–61.5). 58.4% (153 out of 262) of tumours expressed activated c-Src in the nucleus; median histoscore 10 (interquartile range 0–45). High levels (greater than the median value) of activated c-Src expression in the cytoplasm or nucleus was therefore detectable in over 50% (n=153) of all ER-positive breast tumours analysed. 2.7% (7 out of 260, two samples missing) of tumours expressed activated Src in the membrane, median histoscore 0. Because of the low rate of membrane expression observed, it was not deemed appropriate to apply these results to further statistical tests. To confirm that the antibody was able to detect membrane staining 10 prostate tumours were also stained for activated c-Src. Activated c-Src was much more commonly located to the cell membrane of prostate cells compared with the ER-positive breast carcinomas. Figure 2 illustrates the staining patterns observed in the ER-positive breast cancer specimens compared with prostate cancer specimens.


Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer.

Campbell EJ, McDuff E, Tatarov O, Tovey S, Brunton V, Cooke TG, Edwards J - Br. J. Cancer (2008)

The different localisation of activated c-Src, SrcpY416 in prostate and breast tumour samples are shown. In breast tumours, activated c-Src was most commonly present in the cell cytoplasm and the cell nucleus (A and B). In the prostate cancer (C and D), the majority of staining observed for phosphorylated c-Src was located to the membrane, and nuclear expression was rarely observed.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600702&req=5

fig2: The different localisation of activated c-Src, SrcpY416 in prostate and breast tumour samples are shown. In breast tumours, activated c-Src was most commonly present in the cell cytoplasm and the cell nucleus (A and B). In the prostate cancer (C and D), the majority of staining observed for phosphorylated c-Src was located to the membrane, and nuclear expression was rarely observed.
Mentions: A total of 262 ER-positive tumour samples were analysed for activated c-Src expression. 57.3% (150 out of 262) of tumours expressed activated Src in the cytoplasm; median histoscore 20 (interquartile range 0–61.5). 58.4% (153 out of 262) of tumours expressed activated c-Src in the nucleus; median histoscore 10 (interquartile range 0–45). High levels (greater than the median value) of activated c-Src expression in the cytoplasm or nucleus was therefore detectable in over 50% (n=153) of all ER-positive breast tumours analysed. 2.7% (7 out of 260, two samples missing) of tumours expressed activated Src in the membrane, median histoscore 0. Because of the low rate of membrane expression observed, it was not deemed appropriate to apply these results to further statistical tests. To confirm that the antibody was able to detect membrane staining 10 prostate tumours were also stained for activated c-Src. Activated c-Src was much more commonly located to the cell membrane of prostate cells compared with the ER-positive breast carcinomas. Figure 2 illustrates the staining patterns observed in the ER-positive breast cancer specimens compared with prostate cancer specimens.

Bottom Line: High level of nuclear activated Src was significantly associated with improved overall survival (P=0.047) and lower recurrence rates on tamoxifen (P=0.02).Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (P<0.05).On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (P=0.004).

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Sciences and Molecular Pathology, Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.

ABSTRACT
Elevated c-Src protein expression has been shown in breast cancer and in vitro evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan-Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (P=0.047) and lower recurrence rates on tamoxifen (P=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (P<0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (P=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in de novo endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome.

Show MeSH
Related in: MedlinePlus