mRNA expression of ligands of the epidermal-growth-factor-receptor in the uterus

Pfeiffer, Doris; Spranger, J.; Al-Deiri, Michael; Fisseler‐Eckhoff, Annette; Scheidel, P.; Schatz, H.; Jensen, Arne; Pfeiffer, A.

doi:10.1002/(sici)1097-0215(19970807)72:4<581::aid-ijc5>3.0.co;2-m

Cited by 29 publications

(15 citation statements)

References 15 publications

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“…Earlier clinical studies in other disease entities show that potential markers of sensitivity to EGFR TKIs include the presence of EGFR gene amplification, mutations of the EGFR gene, and increased expression of EGFR ligands (Baselga and Arteaga, 2005). Earlier studies have demonstrated significantly higher expression levels of the EGFR ligands TGF-a and amphiregulin in EC compared with normal endometrium (Pfeiffer et al, 1997;Ejskjaer et al, 2007). The roles of EGFR gene amplification or mutations in EC, however, have not yet been studied.…”

Section: Discussionmentioning

confidence: 99%

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

et al. 2008

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Type II endometrial cancers (uterine serous papillary and clear cell histologies) represent rare but highly aggressive variants of endometrial cancer (EC). HER2 and EGFR may be differentially expressed in type II EC. Here, we evaluate the clinical role of HER2 and EGFR in a large cohort of surgically staged patients with type II (nonendometrioid) EC and compare the findings with those seen in a representative cohort of type I (endometrioid) EC. In this study HER2 gene amplification was studied by fluorescence in situ hybridisation (FISH) and EGFR expression by immunohistochemistry. Tissue microarrays were constructed from 279 patients with EC (145 patients with type I and 134 patients with type II EC). All patients were completely surgically staged and long-term clinical follow up was available for 258 patients. The rate of HER2 gene amplification was significantly higher in type II EC compared with type I EC (17 vs 1%, Po0.001). HER2 gene amplification was detected in 17 and 16% of the cases with uterine serous papillary and clear cell type histology, respectively. In contrast, EGFR expression was significantly lower in type II compared with type I EC (34 vs 46%, P ¼ 0.041). EGFR expression but not HER2 gene amplification was significantly associated with poor overall survival in patients with type II EC, (EGFR, median survival 20 vs 33 months, P ¼ 0.028; HER2, median survival 18 vs 29 months, P ¼ 0.113) and EGFR expression retained prognostic independence when adjusting for histology, stage, grade, and age (EGFR, P ¼ 0.0197; HER2, P ¼ 0.7855). We conclude that assessment of HER2 gene amplification and/or EGFR expression may help to select type II EC patients who could benefit from therapeutic strategies targeting both HER2 and EGFR.

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Section: Discussionmentioning

confidence: 99%

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

et al. 2008

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“…The linearity of the amplifications was controlled by densitometric scanning of the gels and plotting of the density against the cycle number. The amplifications were analysed in the linear range as described in detail previously [41]. Shortened standard fragments of these sequences were generated by deleting 50 to 80 bp of internal sequence.…”

Section: Methodsmentioning

confidence: 99%

Cloning and quantitative determination of the human Ca 2+ /calmodulin-dependent protein kinase II (CaMK II) isoforms in human beta cells

et al. 2000

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The Ca 2+ /calmodulin-dependent protein kinase II (CaMK II) is a multifunctional enzyme which is widely expressed from yeast to mammals and occurs in four different isoforms termed a, b, g and d which are derived from different genes [1,2]. The highest concentrations are in the CNS where the aisoform and b-isoform are involved in neurotransmitter release [1,2] whereas the g-isoform and disoform occur in most peripheral cells [3,4] and participate in control of cell cycle, metabolism, gene expression and membrane excitability. Insulin secretion in response to glucose and other nutrient stimuli is dependent on Ca 2+ and CaMK II seems to play an important part in this process [5±7]. Impairment of insulin secretion in response to glucose is an early event in the development of adult Type II (non-insulin-dependent) diabetes mellitus making it Diabetologia (2000) Abstract Aims/hypothesis. The Ca 2+ /calmodulin-dependent protein kinase II (CaMK II) is highly expressed in pancreatic islets and associated with insulin secretion vesicles. The suppression of CaMK II disturbs insulin secretion and insulin gene expression. There are four isoforms of CaMK II, a to d, that are expressed from different genes in mammals. Our aim was to identify the isoforms of CaMK II expressed in human beta cells by molecular cloning from a human insulinoma cDNA library and to assess its distribution in humans. Methods. The previously unknown complete coding sequences of human CaMK IIb and the kinase domain of CaMK IId were cloned from a human insulinoma cDNA library. Quantitative determination of CaMK II isoform mRNA was carried out in several tissues and beta cells purified by fluorescence activated cell sorting and compared to the housekeeping enzyme pyruvate dehydrogenase. Results. We found CaMK IIb occurred in three splice variants and was highly expressed in endocrine tissues such as adrenals, pituitary and beta cells. Liver showed moderate expression but adipose tissue or lymphocytes had very low levels of CaMK IIbmRNA. In human beta cells CaMK IIb and d were expressed equally with pyruvate dehydrogenase whereas tenfold lower expression of CaMK IIg and no expression of CaMK IIa were found. Conclusion/interpretation. Although CaMK IId is ubiquitously expressed, CaMK IIb shows preferential expression in neuroendocrine tissues. In comparison with the expression of a key regulatory enzyme in glucose oxidation, pyruvate dehydrogenase, two of the four CaM kinases investigated are expressed at equally high levels, which supports an important role in beta-cell physiology. These results provide the basis for exploring the pathophysiological relevance of CaMK IIb in human diabetes. [Diabetologia (2000) 43: 465±473]

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“…Showing conservation with the mouse, HB-EGF peaks at the window of implantation (Yoo et al 1997) and ErbB4 is expressed in the trophectoderm in periimplantation human blastocysts (Chobotova et al 2002). In addition, correlative links between elevated expression of Ar and TGF-a with endometrial cancers have been made (Pfeiffer et al 1997).…”

Section: Growth Factorsmentioning

confidence: 99%

Animal models of implantation

Lee

DeMayo²

2004

Reproduction

240

155

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Implantation is an intricately timed event necessary in the process of viviparous birth that allows mammals to nourish and protect their young during early development. Human implantation begins when the blastocyst both assumes a fixed position in the uterus and establishes a more intimate relationship with the endometrium. Due to the impracticalities of studying implantation in humans, animal models are necessary to decipher the molecular and mechanical events of this process. This review will discuss the differences in implantation between different animal models and describe how these differences can be utilized to investigate discrete implantation stages. In addition, factors that have been shown to be involved in implantation in the human and other various animal models including growth factors, cytokines, modulators of cell adhesion, and developmental factors will be discussed, and examples from each will be given.

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mRNA expression of ligands of the epidermal-growth-factor-receptor in the uterus

Cited by 29 publications

References 15 publications

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

Cloning and quantitative determination of the human Ca 2+ /calmodulin-dependent protein kinase II (CaMK II) isoforms in human beta cells

Animal models of implantation

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