A serologically identified tumor antigen encoded by a homeobox gene promotes growth of ovarian epithelial cells

Naora, Honami; Yang, Yupei; Montz, F.J.; Seidman, Jeffrey D.; Kurman, Robert J.; Roden, Richard B.S.

doi:10.1073/pnas.071594398

Cited by 95 publications

(107 citation statements)

References 52 publications

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“…Dysregulation of putative target genes within these lists have been described in ovarian cancer. [74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] E-cadherin and acatenin, components of the cadherin pathway, have previously been found to be dysregulated in metatstatic ovarian carcinoma and serous effusions. [79][80][81] Polymorphisms in cyclin D2 and protein kinase C isoform expression have been linked with prognosis in ovarian carcinoma patients.…”

Section: Discussionmentioning

confidence: 99%

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

et al. 2009

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MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. We characterized the alteration in expression of a select group of microRNAs in primary peritoneal carcinoma relative to matched cases of ovarian serous carcinoma. MicroRNA expression was analysed using semi-quantitative stem-loop RT-PCR on a set of 34 formalin-fixed paraffin-embedded samples. Protein expression of p53 and bcl-2 was quantified in the corresponding tissue microarray. We provide definitive evidence that there is downregulation of a select group of microRNAs in tumours meeting Gynaecological Oncology Group criteria for primary peritoneal carcinoma relative to ovarian serous carcinoma. Specifically, we show decreased p53 expression and downregulation of miR-195 and miR-497 from the microRNA cluster site at chromosome 17p13.1 in primary peritoneal carcinoma relative to ovarian serous carcinoma. miR-195 and miR-497 may have potential roles as tumour-suppressor genes in primary peritoneal tumourigenesis.

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Section: Discussionmentioning

confidence: 99%

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

et al. 2009

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“…Currently, in gynecological field, there have been several reports suggesting that the abnormal expression of particular HOX genes is associated with cervical, ovarian, and endometrial cancers. [16][17][18][19] As for the cervical cancers, several studies have shown a different pattern of expression of specific HOX genes between normal cervix and cervical cancer, including a report which analyzed 39 HOX gene expression profiles. 16 Unfortunately, there have been no studies performing such a comprehensive analysis of the different expression of HOX genes between normal ovary and ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression pattern of the class I homeobox genes in ovarian carcinoma

et al. 2010

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Objective: Although some sporadic reports reveal the link between the homeobox (HOX) genes and ovarian carcinoma, there is no comprehensive analysis of the expression pattern of the class I homeobox genes in ovarian carcinoma that determines the candidate genes involved in ovarian carcinogenesis. Methods: The different patterns of expression of 36 HOX genes were analyzed, including 4 ovarian cancer cell lines and 4 normal ovarian tissues. Using a reverse transcription-polymerase chain reaction (RT-PCR) and quantification analysis, the specific gene that showed a significantly higher expression in ovarian cancer cell lines than in normal ovaries was selected, and western blot analysis was performed adding 7 ovarian cancer tissue specimens. Finally, immunohistochemical and immunocytochemical analyses were performed to compare the pattern of expression of the specific HOX gene between ovarian cancer tissue and normal ovaries. Results: Among 36 genes, 11 genes had a different level of mRNA expression between the cancer cell lines and the normal ovarian tissues. Of the 11 genes, only HOXB4 had a significantly higher level of expression in ovarian cancer cell lines than in normal ovaries (p=0.029). Based on western blot, immunohistochemical, and immunocytochemical analyses, HOXB4 was expressed exclusively in the ovarian cancer cell lines or cancer tissue specimens, but not in the normal ovaries. Conclusion:We suggest HOXB4 may be a novel candidate gene involved in ovarian carcinogenesis.

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“…In addition, antibodies to p53 have been reported in patients with early-stage ovarian or colorectal cancers (10,11). Changes in the level of gene expression in cancer (4,8,12,13) and aberrant expression of tissue-restricted gene products in cancer (14,15) are factors in the development of a humoral immune response in cancer patients. In this respect, serologic analysis of recombinant cDNA expression libraries of tumors with autologous serum has identified some relevant tumor antigens, MAGE (16), SSX2 (17), and NY-ESO-1 (18).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Markers of Ovarian Cancer by High-Throughput Antigen Cloning and Detection on Arrays

et al. 2006

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A noninvasive screening test would significantly facilitate early detection of epithelial ovarian cancer. This study used a combination of high-throughput selection and arraybased serologic detection of many antigens indicative of the presence of cancer, thereby using the immune system as a biosensor. This high-throughput selection involved biopanning of an ovarian cancer phage display library using serum immunoglobulins from an ovarian cancer patient as bait. Protein macroarrays containing 480 of these selected antigen clones revealed 65 clones that interacted with immunoglobulins in sera from 32 ovarian cancer patients but not with sera from 25 healthy women or 14 patients having other benign or malignant gynecologic diseases. Sequence analysis data of these 65 clones revealed 62 different antigens. Among the markers, we identified some known antigens, including RCAS1, signal recognition protein-19, AHNAK-related sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic initiation factor 5A, and casein kinase II, as well as many previously uncharacterized antigenic gene products. Using these 65 antigens on protein microarrays, we trained neural networks on two-color fluorescent detection of serum IgG binding and found an average sensitivity and specificity of 55% and 98%, respectively. In addition, the top 6 of the most specific clones resulted in an average sensitivity and specificity of 32% and 94%, respectively. This global approach to antigenic profiling, epitomics, has applications to cancer and autoimmune diseases for diagnostic and therapeutic studies. Further work with larger panels of antigens should provide a comprehensive set of markers with sufficient sensitivity and specificity suitable for clinical testing in high-risk populations. (Cancer Res 2006; 66(2): 1181-90)

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A serologically identified tumor antigen encoded by a homeobox gene promotes growth of ovarian epithelial cells

Cited by 95 publications

References 52 publications

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

Expression pattern of the class I homeobox genes in ovarian carcinoma

Diagnostic Markers of Ovarian Cancer by High-Throughput Antigen Cloning and Detection on Arrays

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