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| 2. |
- Burger, AM, et al.
(författare)
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The breast cancer-associated gene Di12 has oncogenic activity
- 2003
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Ingår i: Anticancer research. - 1791-7530. ; 23:3A, s. 2027-2033
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Tidskriftsartikel (refereegranskat)abstract
- The breast cancer-associated gene Di12 encodes a novel protein, which was found overexpressed in invasive ductal carcinomas of the breast. In experiments designed to assess the role of the Di12 gene in oncogenesis, the overexpression of 339 N-terminal amino acids of this gene in NIH3T3 cells resulted in cellular transformation and in vivo tumorigenesis. NIH3T3-Di12 tumor cell growth was partly reversible upon Di12 antisense treatment. In addition, transfortnation of the ER + human breast cancer cell line MCF- 7 resulted in hormone independent growth of these tumors in nude mice. Di12 expression in NIH3T3 and MCF-7 tumor cells was confirmed by RT-PCR and mabDi12 immunostaining. Immunohistochemistry using mabDi12 on an arrayed collection of 106 invasive breast tumors further underlined the expression of the gene in over 75% of advanced stage breast cancers. Our data indicate that Di12 expression is oncogenic in in vitro transformation and in vivo tumorigenic assays.
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| 3. |
- Ekberg, Jenny, et al.
(författare)
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Regulation of the cyclin A1 protein is associated with its differential subcellular localization in hematopoietic and leukemic cells
- 2004
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Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 23:56, s. 9082-9089
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Tidskriftsartikel (refereegranskat)abstract
- An important role of the cell cycle regulatory protein cyclin A1 in the development of acute myeloid leukemia (AML) was previously demonstrated in a transgenic mouse model. We have now turned our attention to study specific aspects of the activity and subcellular distribution of cyclin A1 using bone marrow samples from normal donors and patients with AML, as well as leukemic cell lines. We show that the localization of cyclin A1 in normal hematopoietic cells is nuclear, whereas in leukemic cells from AML patients and cell lines, it is predominantly cytoplasmic. In leukemic cell lines treated with all-trans retinoic acid (ATRA), cyclin A1 localized to the nucleus. Further, there was a direct interaction between cyclin A1 and cyclin-dependent kinase 1, as well as a major ATRA receptor, RARalpha, in ATRA-treated cells but not in untreated leukemic cells. Our results indicate that the altered intracellular distribution of cyclin A1 in leukemic cells correlates with the status of the leukemic phenotype.
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| 4. |
- Hedberg, Y, et al.
(författare)
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Cyclin D3 protein content in human renal cell carcinoma in relation to cyclin D1 and clinico-pathological parameters
- 2002
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:2, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Aberrations in the G1/S checkpoint are common in malignancies and are probably important for tumor development. Few G1/S studies have been performed on renal cell carcinoma (RCC) and therefore in this study the cyclin D3 protein content in 80 RCCs and that in 12 corresponding normal kidney cortex tissues are characterized using Western blotting. High cyclin D3 protein content was observed in 16% of the tumors and was significantly associated with aneuploidy, high TNM stage, high nuclear grade, high proliferation and young age. There was no association between tumor cyclin D3 and patient survival. The cyclin D3 overexpression was confirmed by immunohistochemical staining of 72 tumors, showing both nuclear and cytoplasmic localization of cyclin D3 in a fraction of the tumors. The cyclin D1 content has earlier been characterized in this tumor material and there was no relation between cyclin D1 and cyclin D3 protein expression. In summary, a fraction of the tumors overexpressed cyclin D3, supporting that various aberrations in the G1/S transition are implicated in RCCs.
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| 5. |
- Hedberg, Y, et al.
(författare)
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Cyclin E and P27 protein content in human renal cell carcinoma: Clinical outcome and associations with cyclin D
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 102:6, s. 601-607
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Tidskriftsartikel (refereegranskat)abstract
- Aberrations in the GI-S transition have been observed in several malignancies, suggesting that cell cycle defects are linked to the activation of oncogenes and inactivation of suppressor genes involved in the transformation process. The frequency of GI/S aberrations in human renal cell carcinoma (RCC) has not been fully clarified. We have therefore analyzed the cyclin E content, using Western blotting, in 79 RCC and 12 corresponding kidney cortex tissues as well as the fraction of p27-positive cells in 73 RCCs, using immunohistochemistry. Most of the tumors (65%) exhibited higher cyclin E levels than corresponding normal kidney cortex tissues. However, only a small fraction of the tumors (3 of 80) had excessive levels of cyclin E when cyclin E levels were compared with proliferation. Cyclin E levels higher than the median value were associated with aneuploicly (p = 0.025), high stage (p = 0.027), high grade (p = 0.013) and high erythrocyte sedimentation rate (ESR; p = 0.005). Cyclin E was further inversely correlated with cyclin D1 (p = 0.023) and positively correlated with cyclin D3 (p = 0.003). Most tumors (76%) demonstrated a normal fraction of p27-positive cells. There was an inverse correlation between p27 positivity and tumor size (p = 0.007), despite a lack of correlation between p27 and proliferation. Patients with p27 low tumors had a poor survival (p = 0.002). There was no correlation between p27 and cyclin E levels. In summary, the results suggest that protein expression of cyclin E and/or p27 is linked to tumor behavior. (C) 2002 Wiley-Liss, Inc.
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| 6. |
- Hedberg, Y, et al.
(författare)
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Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 88:9, s. 1417-1423
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Tidskriftsartikel (refereegranskat)abstract
- Aberrations in the GI/S transition of the cell cycle have been observed in many malignancies and seem to be critical in the transformation process. Few studies have delineated the presence of GI/S regulatory defects and their clinical relevance in renal cell carcinoma (RCC). Therefore, we have examined the protein contents of cyclin D 1, D3, E, and p27 in 218 RCCs, using tissue microarray and immunohistochemistry. The results from a subset of tumours were confirmed by Western blotting and immunohistochemical staining of regular tissue sections. Interestingly, low protein contents of cyclin D I and p27 were associated with high nuclear grade, large tumour size, and poor prognosis for patients with conventional tumours. We further observed substantial differences in the pattern of GI/S regulatory defects between the different RCC subtypes. The majority of both conventional and papillary cases expressed p27; however, chromophobe tumours generally lacked p27 staining. In addition, conventional RCCs often expressed high cyclin DI protein levels, while papillary RCCs exhibited high cyclin E. In summary, we have shown that GI/S regulatory defects are present in RCC and are associated with clinico-pathological parameters. The pattern of cell cycle regulatory defects also differed between RCC subtypes. (C) 2003 Cancer Research UK.
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| 10. |
- Kronblad, Åsa, et al.
(författare)
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Regional cyclin D1 overexpression or hypoxia correlate inversely with heterogeneous oestrogen receptor-alpha expression in human breast cancer.
- 2003
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Ingår i: In Vivo. - 0258-851X. ; 17:4, s. 311-8
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Tidskriftsartikel (refereegranskat)abstract
- Substance P (SP) has been implicated in the pathophysiology of ulcerative colitis (UC) and it has been suggested that blocking of its effect would be advantageous in this disease. Eosinophils have also been implicated in the pathophysiology of UC. In the present study, specimens from the sigmoid colon of UC patients were investigated by the use of antisera against SP and the neurokinin-1 receptor (NK-1R) and staining for demonstration of eosinophils. The degrees of SP innervation and NK-1R immunoreaction, as well as the levels of eosinophil infiltration, varied between different patients. Interestingly, NK-1R immunoreaction in the epithelium was often seen to be the most marked where there were numerous eosinophils in the underlying mucosa and where the mucosa showed a marked morphologic derangement. The observations suggest that there are marked fluctuations in effects of SP and eosinophils during the disease. The infiltrating eosinophils may be involved in the destruction of the mucosal tissue. Furthermore, for the majority of cases where there is marked derangement of the mucosa, it is apparent that there is an upregulation of the NK-1 receptor in the epithelium in parallel with the infiltration of the eosinophils.
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