A Receptor Tyrosine Kinase, UFO/Axl, and Other Genes Isolated by a Modified Differential Display PCR Are Overexpressed in Metastatic Prostatic Carcinoma Cell Line DU145

Jacob, Alexander; Kalapurakal, John A.; Davidson, William R.; Kandpal, Geeta; Dunson, N.; Prashar, Yatindra; Kandpal, Raj P.

doi:10.1046/j.1525-1500.1999.99034.x

Cited by 41 publications

(35 citation statements)

References 14 publications

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“…Their increased expressions might be the direct or indirect causes of cell proliferation of the MCV152 cell line with FSH treatment. Among them, overexpression of AXL-RTK has been known in metastatic colon and prostatic cancers, 23,24 and our study is the first one to document in OSE cells. Further investigations, especially on potential roles of those oncogenes in ovarian carcinogenesis, should be required.…”

Section: Discussionmentioning

confidence: 53%

Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells

Liu

Chen

et al. 2004

Intl Journal of Cancer

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Ovarian cancer (OC) is one of the leading causes of death in patients with gynecologic malignancies. The vast majority of ovarian cancers have a cell origin of ovarian surface epithelium (OSE), which is derived from Mullerian epithelium covering embryonic gonads. Since the incidence of OC sharply increases after menopause, critical roles of gonadotropins and their receptors in ovarian carcinogenesis are speculated by investigators. 1 Follicle stimulating hormone (FSH), through interaction with its specific receptor, FSHR, plays an essential role in mammalian reproduction and ovarian folliculogenesis. 2 Binding of FSH to FSHR results in adenylyl cyclase activation leading to cAMP synthesis, associated with intracellular rise of Ca 2ϩ , activation of protein kinase A (PKA) and other downstream signal transduction pathways. [2][3][4][5][6] It has been reported that FSH treatment stimulates cell proliferation on normal human OSE cells, immortalized OSE cells and OC cell lines. 7,8 However, little has been known on the effects of FSH in the process of tumorigenesis and growth stimulation on human OSE at molecular levels.In this study, we first determined FSHR expression levels quantitatively in human ovarian normal and neoplastic tissues. Then the effects of FSH treatment on cell proliferation were examined using human OSE cell lines as well as Chinese hamster ovary (CHO) cell lines permanently transfected with human FSHR. Finally, gene expression profiles for FSH treatment were analyzed by cDNA MicroArray using a selected human OSE cell line that has best growth response to FSH treatment from cell proliferation assays. MATERIAL AND METHODS

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Section: Discussionmentioning

confidence: 53%

Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells

Liu

Chen

et al. 2004

Intl Journal of Cancer

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“…Herein, we used phosphotyrosine immunoaffinity and mass spectrometry to identify activated tyrosine kinase proteins in mesothelioma (Figure 1): these studies demonstrated AXL activation, which we show to be a frequent event in mesothelioma cell lines and mesothelioma surgical specimens, but not in normal mesothelial cells. Notably, AXL expression, overall, was even stronger in mesothelioma than in various other cancer types that have been reported to feature high levels of AXL expression (Figure 2a)-including prostate cancer, melanoma and colon carcinoma (Quong et al, 1994;Craven et al, 1995;Jacob et al, 1999). We show that AXL expression and activation are particularly strong in the spindle-cell subtypes of mesothelioma, which are known to be associated with short survival (Figure 2c).…”

Section: Discussionmentioning

confidence: 54%

“…AXL is characterized by a unique extracellular composition consisting of immunoglobulin-like and fibronectin-type III-like domains, which are also found in adhesion molecules of the cadherin and immunoglobulin superfamily, therefore suggesting that AXL might regulate cell adhesion (Burchert et al, 1998). Other evidence is consistent with roles of AXL in tumor cell invasion, metastasis and survival (Jacob et al, 1999;Holland et al, 2005;Mahadevan et al, 2007).…”

Section: Introductionmentioning

confidence: 69%

“…We show that AXL expression and activation are particularly strong in the spindle-cell subtypes of mesothelioma, which are known to be associated with short survival (Figure 2c). Various recent studies implicate AXL as an oncogenic factor in advanced solid tumors: AXL is overexpressed in highly invasive lung adenocarcinoma cell lines, metastatic DU145 prostate cancer models and metastatic colon tumors (Craven et al, 1995;Jacob et al, 1999;Shieh et al, 2005). These and other studies suggest that AXL overexpression promotes invasiveness (Lay et al, 2007;Tai et al, 2008;Li et al, 2009).…”

Section: Discussionmentioning

confidence: 86%

“…AXL was first identified as a transforming gene in chronic myeloid leukemia (Janssen et al, 1991;O'Bryan et al, 1991), but is also overexpressed in metastatic colon and prostate cancer, thyroid carcinoma, breast cancer and melanoma (Quong et al, 1994;Craven et al, 1995;Ito et al, 1999;Jacob et al, 1999;Meric et al, 2002). Various studies have demonstrated roles of GAS6/AXL in regulating cell growth and survival in normal and cancer cells (Stitt et al, 1995;Wimmel et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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AXL regulates mesothelioma proliferation and invasiveness

et al. 2010

Oncogene

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Mesothelioma is an asbestos-associated and notoriously chemotherapy-resistant neoplasm. Activation of the receptor tyrosine kinases (RTKs), epidermal growth factor receptor and MET, has been described in subsets of mesothelioma, suggesting that TKs might represent therapeutic targets in this highly lethal disease. We employed proteomic screening by phosphotyrosine immunoaffinity purification and tandem mass spectrometry to characterize RTK activation in mesothelioma cell lines. These assays demonstrated expression and activation of the AXL protein, which is an RTK with known oncogenic properties in non-mesothelial cancer types. AXL was expressed and activated strongly in 8 of 9 mesothelioma cell lines and 6 of 12 mesothelioma biopsies, including each of 12 mesotheliomas with spindle-cell histology. Somatic AXL mutations were not found, but all mesotheliomas expressed an alternatively spliced AXL transcript with in-frame deletion of exon 10, and six of seven mesothelioma cell lines expressed the AXL ligand, growth arrest-specific 6 (GAS6). GAS6 expression appeared to be functionally relevant, as indicated by modulation of AXL tyrosine phosphorylation by knockdown of endogeneous GAS6, and by administration of exogenous GAS6. AXL silencing by lentivirus-mediated short hairpin RNA suppressed mesothelioma migration and cellular proliferation due to G1 arrest. The AXL inhibitor DP-3975 inhibited cell migration and proliferation in mesotheliomas with strong AXL activation. DP-3975 response in these tumors was characterized by inhibition of PI3-K/AKT/mTOR and RAF/MAPK signaling. AXL inhibition suppressed mesothelioma anchorage-independent growth, with reduction in colony numbers and size. These studies suggest that AXL inhibitors warrant clinical evaluation in mesothelioma.

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Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and Mer in the developing rat central nervous system

2000

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Tyro-3, Axl, and Mer are three related receptor protein-tyrosine kinases (RPTKs) characterized by an extracellular domain exhibiting significant amino acid sequence similarity to neural cell adhesion molecules. The molecule Gas6 (for growth arrest-specific gene-6) has been shown to activate each of these receptors. Gas6 is expressed extensively in the central nervous system (CNS), suggesting that interactions between Gas6 and its receptors are likely to have physiologically relevant functions. To identify and localize the relevant Gas6/RPTK pairs, we have characterized the developmental expression of Tyro-3, Axl, and Mer in rat CNS using blotting and mRNA in situ hybridization analyses. Throughout development, Tyro-3 was the most widely expressed of the three receptors in the CNS, with Axl and Mer detected in only a limited number of sites in the adult. Tyro-3 expression was low in the embryo and increased markedly during early postnatal stages, with a time course paralleling that of synaptogenesis. Axl and Mer were expressed at low but relatively constant levels throughout development. In the cerebellum, all three receptors were found in Purkinje cells, and Tyro-3 was also detected in both granule neurons and Bergmann glia. Insofar as Gas6 has been previously shown to also be expressed by Purkinje cells, it may be engaged in both autocrine and paracrine signaling. The three receptors were also detected in cerebellar white matter, primarily during myelination. In the cortex, Tyro-3 was expressed at high levels during postnatal development and in the adult. Beginning at P6 in the hippocampus, Tyro-3 was expressed at high levels in CA1 pyramidal neurons and at lower levels in CA3 and was not detected in dentate granule neurons. Axl and Mer were found in the molecular layer of the dentate gyrus and were absent from the pyramidal and dentate granule neurons. In that Gas6 is expressed throughout the pyramidal cell layer, it may activate these cells in both an autocrine and a paracrine manner. These studies provide initial clues for elucidating the cellular functions of the Axl subfamily members and suggest potential complex Gas6/RPTK as well as RPTK/RPTK signaling interactions in the mature and developing CNS.

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A Receptor Tyrosine Kinase, UFO/Axl, and Other Genes Isolated by a Modified Differential Display PCR Are Overexpressed in Metastatic Prostatic Carcinoma Cell Line DU145

Cited by 41 publications

References 14 publications

Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells

Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells

AXL regulates mesothelioma proliferation and invasiveness

Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and Mer in the developing rat central nervous system

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