| 1. |
- Magnusson, Cecilia, et al.
(författare)
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Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients.
- 2011
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; Okt, s. 9-22
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Tidskriftsartikel (refereegranskat)abstract
- The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. Here we have determined the expression of pro-inflammatory cysteinyl leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect on breast cancer cell functions related to tumor progression. Patients with breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels exhibited increased risk of cancer-induced death in univariate analysis for both the total patient group (HR = 2.88, 95% CI 1.11-7.41), as well as patients with large (>20mm) tumors (HR = 5.08, 95% CI 1.39-18.5). Multivariate analysis revealed that patients with large tumors exhibiting high CysLT(1)R and low CysLT(2)R expression levels had a significantly reduced survival, also when adjusted for established prognostic parameters (HR = 7.51, 95% CI 1.83-30.8). In patients with large (>20mm) tumors, elevated CysLT(2)R expression predicted an improved five-year survival (log-rank test P = 0.04). Surprisingly, for longer time periods this prognostic value was lost. This disappearance coincided with the termination of hormonal treatment. Tamoxifen preserved and even induced transcription of CysLT(2)R, but not CysLT(1)R, in ER-positive MCF-7 breast cancer cells. This elevated CysLT(2)R expression decreased, even below the level of untreated cells, when tamoxifen was withdrawn. CysLT(2)R signaling reduced MCF-7 cell migration, but had no effect on either proliferation or apoptosis. Our data indicate that low CysLT(1)R together with high CysLT(2)R expression levels might be useful parameters in prognostication and treatment stratification of breast cancer patients.
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| 2. |
- Tassidis, Helena, et al.
(författare)
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Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer
- 2010
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 126:10, s. 2296-2307
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Tidskriftsartikel (refereegranskat)abstract
- The protein tyrosine kinase (PTK) receptors and cytosolic signaling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in regulation of growth of the benign and malignant prostate gland. Here, we studied expression of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in human prostatic tissues. SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared with PC3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation, whereas overexpression of SHP-1 by means of transient and stable transfection in PC3 cells led to a decrease in proliferation. Corresponding changes were observed in cyclin D1 expression. We further demonstrate that LNCaP and PC3 cells respond differently to IL-6 stimulation. SHP-1 overexpression in PC3 cells reversed IL-6 stimulation of proliferation, whereas in SHP-1-silenced LNCaP cells, IL-6 inhibition of proliferation was not affected. In addition, IL-6 treatment led to higher levels of phosphorylated STAT3 in SHP-1-silenced LNCaP cells than in control cells. Next, SHP-1 expression in human prostate cancer was analyzed by immunohistochemical staining of tissue microarrays comprising tumor specimens from 100 prostate cancer patients. We found an inverse correlation between the tumor level of SHP-1 expression and time to biochemical recurrence and clinical progression among prostate cancer patients. In conclusion, our results suggest that a decreased level of SHP-1 expression in prostate cancer cells is associated with a high proliferation rate and an increased risk of recurrence or clinical progression after radical prostatectomy for localized prostate cancer.
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| 3. |
- Tassidis, Helena, et al.
(författare)
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Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer
- 2009
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 69:9 Supplement, s. LB-257-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The protein tyrosine kinase (PTK) receptors and cytosolic signalling proteins as well as the protein tyrosine phosphatases (PTP) have important roles in regulation of growth and function of the benign and malignant prostate gland. Here we studied the expression levels and functions of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in benign and malignant human prostatic tissues. We found that SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared to PC-3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation as measured by thymidine incorporation, whereas in PC3 cells in which SHP1 was overexpressed by transient transfection proliferation rate was decreased. We also examined SHP-1 expression in prostate cancer by immunohistochemical staining of tissue microarrays comprising tumor specimens from 122 prostate cancer patients. We found an inverse correlation between SHP-1 staining intensity and the time to biochemical recurrence as measured by a rise in the serum level of prostate-specific antigen (PSA) in prostate cancer patients. In conclusion, our results suggest that a low level of SHP-1 expression in prostate cancer cells is associated with high proliferation rate and with an increased risk of biochemical recurrence after radical prostatectomy for localized prostate cancer.
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| 4. |
- Tassidis, Helena, et al.
(författare)
-
Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer
- 2010
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:10, s. 2296-2307
-
Tidskriftsartikel (refereegranskat)abstract
- The protein tyrosine kinase (PTK) receptors and cytosolic signaling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in regulation of growth of the benign and malignant prostate gland. Here, we studied expression of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in human prostatic tissues. SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared with PC3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation, whereas overexpression of SHP-1 by means of transient and stable transfection in PC3 cells led to a decrease in proliferation. Corresponding changes were observed in cyclin D1 expression. We further demonstrate that LNCaP and PC3 cells respond differently to IL-6 stimulation. SHP-1 overexpression in PC3 cells reversed IL-6 stimulation of proliferation, whereas in SHP-1-silenced LNCaP cells, IL-6 inhibition of proliferation was not affected. In addition, IL-6 treatment led to higher levels of phosphorylated STAT3 in SHP-1-silenced LNCaP cells than in control cells. Next, SHP-1 expression in human prostate cancer was analyzed by immunohistochemical staining of tissue microarrays comprising tumor specimens from 100 prostate cancer patients. We found an inverse correlation between the tumor level of SHP-1 expression and time to biochemical recurrence and clinical progression among prostate cancer patients. In conclusion, our results suggest that a decreased level of SHP-1 expression in prostate cancer cells is associated with a high proliferation rate and an increased risk of recurrence or clinical progression after radical prostatectomy for localized prostate cancer.
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| 5. |
- Topi, Geriolda, et al.
(författare)
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Association of the oestrogen receptor beta with hormone status and prognosis in a cohort of female patients with colorectal cancer
- 2017
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 83, s. 279-289
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Tidskriftsartikel (refereegranskat)abstract
- Background The oestrogen receptor beta (ERβ) is the predominant oestrogen receptor in the normal colon mucosa and has been reported to exert anti-proliferative and pro-apoptotic effects. However, the role of ERβ in colorectal cancer (CRC) progression remains unclear. Aim To investigate the role of ERβ and its association with hormone status and lifestyle indicators in a female cohort of patients with CRC. Methods Tissue microarrays of primary CRC tumour samples from 320 female patients were conducted with a monoclonal anti-ERβ antibody. The staining intensity was evaluated using immunohistochemistry. The association of ERβ expression with overall survival, disease-free survival, hormone status and lifestyle was evaluated, and effect estimators with 95% confidence intervals (CIs) were reported. Results Among the 314 samples with successfully detected ERβ, 182 (58%) had low expression and 132 (42%) had high expression. The Cox multivariate analysis indicated that patients with high ERβ expression had a decreased risk of overall mortality by 50% (hazard ratio [HR], 0.50; CI, 0.30–0.83) and of cancer recurrence by 76% (HR, 0.24; CI, 0.11–0.52) after adjusting for age, tumour-node-metastasis stage and tumour intravascular invasion. Furthermore, high ERβ expression was significantly correlated with shorter breastfeeding time and longer use of hormone replacement therapy. No association was found between ERβ expression and lifestyle indicators. Conclusion Elevated ERβ expression is independently associated with a better prognosis and hormone status but not lifestyle indicators in female CRC patients.
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