Expression of Progranulin (Acrogranin/PCDGF/Granulin-Epithelin Precursor) in Benign and Malignant Ovarian Tumors and Activation of MAPK Signaling in Ovarian Cancer Cell Line

Cuevas-Antonio, Rocio; Cancino, Claudia Marcela Hernández; Arechavaleta-Velásco, Fabián; Andrade, Arturo; Barron, Lindsey; Estrada, Isaac; Fernandez, R.; Olguín, Valeria; Ruíz, Santiago; Imani, Farhad; Zeferino-Toquero, Moises; Ulloa‐Aguirre, Alfredo; Gerton, George L.; Dı́az-Cueto, Laura

doi:10.3109/07357900903346455

Cited by 47 publications

(41 citation statements)

References 30 publications

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“…PGRN has been investigated as a potential prognostic marker for ovarian cancer. A significantly worse overall survival for patients with high PGRN mRNA expression in ovarian cancers was demonstrated [34]. High PGRN protein expression in ovarian effusion tumor cells correlated to a better overall survival, while elevated PGRN expression in the tumor stromal cells correlated with worse overall survival [31].…”

Section: Ovarian Cancermentioning

confidence: 99%

“…Over production of PGRN frequently confers a more aggressive phenotype on cancer cells in vitro, as assessed by parameters such as anchorage-independent growth, improved survival or invasion assays (for examples, see refs [34,36,38,40,45,46,57,[62][63][64][65][66]). Increasing the production of PGRN in poorly tumorigenic cells often results in a more malignant phenotype following transplantation into mice.…”

Section: Pgrn Promotes Tumorigensis In Experimental Modelsmentioning

confidence: 99%

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The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy

Zhang¹

2012

J Carcinogene Mutagene

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Progranulin (PGRN) is a secreted glycoprotein growth factor with tumorigenic roles in a variety of tumors including, among others, breast, ovarian, prostate, bladder, and liver cancer. In some patients, for example with breast, ovarian or liver cancers, high PGRN expression in tumors correlated with a worse outcome. Studies using cell lines and animal models provide evidence that PGRN promotes tumor cell proliferation, migration and survival, and induces drug resistance. Increasing or decreasing PGRN production enhances or inhibits respectively the growth of PGRN-sensitive tumors in vivo. PGRN activity is associated with p44/42 mitogen-activated protein kinase as well as phosphatidylinositol 3-kinases signaling pathways. In addition, PGRN may stimulate the formation of the tumor stroma. As an extracellular regulator of tumorgenesis, PGRN is a potential therapeutic target and biomarker of prognosis in the treatment of various cancers.

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Section: Ovarian Cancermentioning

confidence: 99%

Section: Pgrn Promotes Tumorigensis In Experimental Modelsmentioning

confidence: 99%

The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy

Zhang¹

2012

J Carcinogene Mutagene

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“…These differences are likely to translate to the protein level, since a close correlation between progranulin mRNA and protein has been demonstrated in other tumors (Li-qin et al, 2011;Cuevas-Antonio et al, 2010). Also, there is a need for additional non-invasive and simple diagnostic tools with a high sensitivity and specificity for the detection of cancer bladder .…”

Section: Discussionmentioning

confidence: 98%

“…It is expressed at higher levels than normal in a number of cancers of different types including carcinomas, sarcomas, gliomas and myelomas (Li-qin et al, 2011). Also, increased expression of progranulin has been associated with tumor progression and invasiveness in several cancers, including ovarian cancer (Devoogdt et al, 2009;Cuevas-Antonio et al, 2010), renal carcinoma (Donald et al, 2001), hepatocellular carcinoma (Ho et al, 2008), myeloma (Wang et al, 2006), prostate cancer (Monami et al, 2009), endometrial cancer (Jones et al, 2006), breast cancer (Li-qin et al, 2011) and lung cancer (Stewart, 2010;Hu et al, 2006) based on a variety of experimental approaches. So, this diversity of anatomical sites, including cancer bladder detected in this study, is suggestive of a significant role for progranulin in tumor biology (Zhang and Bateman, 2011).…”

Section: Discussionmentioning

confidence: 99%

Role of Progranulin Gene Expression as a Molecular Biomarker for Bladder Cancer

Anas¹

2012

American Journal of Biochemistry and Biotechnology

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Bladder cancer is the second most common cancer of the urinary system. Early diagnosis of this tumor and estimation of risk of future progression has a significant impact on prognosis. Although there are several molecular markers for the diagnosis and prognosis for this tumor, their accuracy is not ideal. Progranulin is a growth factor that may play a critical role in bladder cancer. Previous reports have shown that progranulin is essential for cellular proliferation. In this study, we examined whether progranulin gene expression can be a novel molecular marker for bladder cancer and evaluated its potential suitability as a urinary biomarker for bladder cancer diagnosis. Expression of progranulin gene in tissue and urine sediment of normal and bladder cancer samples was performed by semi-quantitative reverse transcription-PCR. Also, progranulin level was estimated in 90 voided urine samples, including 65 bladder cancer patients and 25 healthy volunteers using the quantitative enzyme immunoassay technique. Significant over-expression of progranulin was observed in bladder cancer cases. This over-expression was correlated with the stage and grade of the cancer. The urinary progranulin level was significantly higher in bladder cancer patients compared to control subjects (means: 18.39±0.56 and 9.17±0.41 ng mL −1 , respectively; p<0.001). Furthermore, the urinary progranulin level at cut off value = 11.275 has a sensitivity = 93.8% and a specificity = 84% for cancer bladder diagnosis. Urinary progranulin may be considered as a simple, noninvasive test with acceptable sensitivity and specificity for bladder cancer diagnosis and may greatly improve the current diagnosis based on cytology. However, this is a preliminary study that opens the window for further researches to fully validate its results in progranulin and cancer bladder research.

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“…The wide expression of ADAM15 and acrogranin in tissues and cells (Edwards et al 2008, De Muynck & Van Damme 2011 suggests that the ADAM15-acrogranin complex may be of broad significance in many biological processes besides fertilization, like for instance, development and cancer. ADAM15 and acrogranin have been related to cell adhesion exerting apoptosis resistance and survival effects on different cell lines (He et al 2002, Guerra et al 2007, Ryan et al 2009, Bö hm et al 2010, Cuevas-Antonio et al 2010, Rosen et al 2011, Hou et al 2013. These effects could be related to the modulation of focal adhesion kinase signaling through activation of Src (Fried et al 2012, Bö hm et al 2013 as well as the formation of a complex involving paxillin, FAK, and ERK (He et al 2002, Monami et al 2006, Ryan et al 2009).…”

Section: P<0002mentioning

confidence: 99%

ADAM15 participates in fertilization through a physical interaction with acrogranin

et al. 2014

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Mammalian fertilization is completed by direct interaction between sperm and egg. This process is primarily mediated by both adhesion and membrane-fusion proteins found on the gamete surface. ADAM1, 2, and 3 are members of the ADAMs protein family, and have been involved in sperm-egg binding. In this study, we demonstrate the proteolytic processing of ADAM15 during epididymal maturation of guinea pig spermatozoa to produce a mature form a size of 45 kDa. We find that the size of the mature ADAM15, 45 kDa, in cauda epididymal spermatozoa indicates that the pro-domain and metalloprotease domain are absent. In addition, using indirect immunofluorescence, ADAM15 was found throughout the acrosome, at the equatorial region and along the flagellum of guinea pig spermatozoa. After acrosome reaction, ADAM15 is lost from the acrosomal region and retained in the equatorial region and flagellum. In this study, we also report the first evidence of a complex between ADAM15 and acrogranin. By immunoprecipitation, we detected a protein band of 65 kDa which co-immunoprecipated together ADAM15. Analysis of the N-terminal sequence of this 65 kDa protein has revealed its identity as acrogranin. In addition, using cell-surface labeling, ADAM15 was found to be present on the cell surface. Assays of heterologous fertilization showed that the antibody against acrogranin inhibited the sperm-egg adhesion. Interestingly, ADAM15 and acrogranin were also found associated in two breast cancer cell lines. In conclusion, our results demonstrated that ADAM15 and acrogranin are present on and associated with the surface of guinea pig spermatozoa; besides both proteins may play a role during sperm-egg binding.

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Expression of Progranulin (Acrogranin/PCDGF/Granulin-Epithelin Precursor) in Benign and Malignant Ovarian Tumors and Activation of MAPK Signaling in Ovarian Cancer Cell Line

Cited by 47 publications

References 30 publications

The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy

The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy

Role of Progranulin Gene Expression as a Molecular Biomarker for Bladder Cancer

ADAM15 participates in fertilization through a physical interaction with acrogranin

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