1.
2.
Burger, AM, et al.
(författare)
The breast cancer-associated gene Di12 has oncogenic activity
2003
Ingår i: Anticancer research. - 1791-7530. ; 23:3A, s. 2027-2033
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.
3.
Hedberg, Y, et al.
(författare)
Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray
2003
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 88:9, s. 1417-1423
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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6.
Kronblad, Åsa, et al.
(författare)
Regional cyclin D1 overexpression or hypoxia correlate inversely with heterogeneous oestrogen receptor-alpha expression in human breast cancer.
2003
Ingår i: In Vivo. - 0258-851X. ; 17:4, s. 311-8
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.
7.
Loden, M, et al.
(författare)
C-erbB2, p27 and G1/S aberrations in human primary breast cancer
2003
Ingår i: Anticancer research. - 1791-7530. ; 23:3A, s. 2053-2061
Tidskriftsartikel (refereegranskat) abstract
Background: C-erbB2 is overexpressed in approximately one-fourth of human breast cancers. In spite of numerous reports suggesting a connection of c-erbB2 overexpression with cell cycle regulation through p27, D cyclins and c-myc. the relationship between c-erbB2 and proliferation through de-regulation of the pRb pathway in primaty breast cancer has not been fully clarified. Materials and Methods: For this purpose we compared the expression of c-erbB2 in a total of 10.5 primary breast tumours with a variety of cell cycle proteins and clinical parameters. Results: GerbB2 was strongly con-elated with down-regulation of p27 and overexpression of c-erbB2 was', as expected, associated with poor survival. However, there was no correlation with proliferation. There was, nevertheless, an association between c-erbB2 and proliferation in certain subtypes of breast cancer, as in oestrogen-receptor-positive e tumours, tumours with high cyclin D1 and in tumours with an overall linear pRb pathway, i.e. tumours with a preserved linearity between cyclin D1, pRb phosphorylation and proliferation. Conclusion: Our results suggest that c-erbB2 may have alternative functions in different subtypes of breast cancer, and further stress that c-erbB2, in addition to promoting proliferation, also functions through other mechanisms in breast cancer.
8.
Ryden, L, et al.
(författare)
Tumor specific VEGF-A and VEGFR2/KDR protein are co-expressed in breast cancer
2003
Ingår i: Breast Cancer Research and Treatment. - 1573-7217 .- 0167-6806. ; 82:3, s. 147-154
Tidskriftsartikel (refereegranskat) abstract
Angiogenesis is a prognostic indicator in primary breast cancer regulated by specific angiogenic factors and their receptors. Vascular endothelial growth factor-A (VEGF-A), so far considered the most important, acts through dimerization of the receptor VEGFR2/KDR within the receptor tyrosine kinase family of VEGF receptors. In order to study the interplay between VEGF-A and VEGFR2/KDR in breast cancer we evaluated their expression by immunohistochemistry in 102 breast cancers organized in a tumor tissue array system allowing semi-quantitative evaluation of cytoplasmatic staining intensity. In addition, VEGF-A(165) was analyzed by an enzyme immuno assay (ELISA) in protein extracts prepared from frozen tissue from 98 of 102 tumors included in the array. Cytoplasmatic staining of VEGF of varying intensity was observed in all samples and correlated with the ELISA results of VEGF content (p=0.007). Interestingly, VEGFR2/KDR expression correlated with VEGF expression using immunohistochemistry, indicating that VEGF and VEGFR2/KDR may be co-expressed in breast cancer. Furthermore, high levels of VEGF-A(165) in the protein extracts was associated with impaired short time survival but not long term survival whereas immunohistochemically assessed VEGF and VEGFR2/KDR were not significantly associated with survival. In summary, immunohistochemically based analysis of VEGF using a tumor tissue array system seems to be a useful method for VEGF quantification in breast cancer here validated using an ELISA based method. The tumor tissue array system enables opportunities of simultaneous analysis of markers engaged in angiogenesis justifying further studies using larger series of tumors.
9.
Seth, A, et al.
(författare)
Gene expression profiling of ductal carcinomas in situ and invasive breast tumors
2003
Ingår i: Anticancer research. - 1791-7530. ; 23:3A, s. 2043-2051
Tidskriftsartikel (refereegranskat) abstract
Comparative and functional genomics are powerful tools to advance the understanding of the molecular basis of cancer. It is believed that genes are epigenetically regulated and, thus, each tumor type and stage will be characterized by a gene expression fingerprint. In this study we identified genes that are differentially expressed in ductal carcinoma in situ and invasive ductal carcinoma of the breast. To isolate genes that are associated with progression of breast cancer we performed differential display and subtractive cloning procedures using matched RNA from normal and tumor tissue. cDNA microarray analysis generated gene expression profiles typical of the transition front in situ to invasive breast cancer when we used mRAA extracted from a case of low-to intermediate-grade DCIS and a case of high-grade DC1S/IDC. cDNAs from these samples were the probes in a cDNA microarray hybridization to 9183 unique cDAAs representing 8507 genes. Signals from both transcriptomes were obtained for 8083 genes, and the balanced differential expression values between pure DCIS and DCIS/invasive tumors revealed 303 distinct cDNAs with a ratio of > 2. Interferon inducible genes were found to be expressed at the highest level in the pure DCIS sample. Genes most abundantly expressed in the invasive tumor were immunoglobulin heavy constant gamma 3 and calgranulin B. Further analysis of RNA and protein expression in breast tumor cell lines and patient tissue samples revealed that: IGFBP-rP1 is down-regulated in invasive tumors whereas cyclin I protein is regulated by ubiquitination and is associated with ER-negative breast cancers. Conclusion: The known and novel genes discussed here represent targets for molecular characterization during breast cancer development as well as,for designing novel strategies for diagnosis and treatment.
