Androgen Regulates<i>ADAMTS15</i>Gene Expression in Prostate Cancer Cells

Molokwu, Chidi N.; Adeniji, O O; Chandrasekharan, Shankar; Hamdy, Freddie C.; Buttle, David J.

doi:10.3109/07357907.2010.489538

Cited by 17 publications

(21 citation statements)

References 52 publications

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“…Evidence, however, is emerging that ADAMTS proteins can also function as tumor suppressors. ADAMTS1, ADAMTS12, and ADAMTS15 act as tumor suppressors in prostate, colon, and breast cancer (Porter et al 2006;Moncada-Pazos et al 2009;Viloria et al 2009;El Hour et al 2010;Molokwu et al 2010). Our genetic evidence shows CG4096 has an inhibitory effect on Egfr activity.…”

Section: Discussionmentioning

confidence: 99%

New Negative Feedback Regulators of Egfr Signaling inDrosophila

et al. 2012

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The highly conserved epidermal growth factor receptor (Egfr) pathway is required in all animals for normal development and homeostasis; consequently, aberrant Egfr signaling is implicated in a number of diseases. Genetic analysis of Drosophila melanogaster Egfr has contributed significantly to understanding this conserved pathway and led to the discovery of new components and targets. Here we used microarray analysis of third instar wing discs, in which Egfr signaling was perturbed, to identify new Egfrresponsive genes. Upregulated transcripts included five known targets, suggesting the approach was valid. We investigated the function of 29 previously uncharacterized genes, which had pronounced responses. The Egfr pathway is important for wing-vein patterning and using reverse genetic analysis we identified five genes that showed venation defects. Three of these genes are expressed in vein primordia and all showed transcriptional changes in response to altered Egfr activity consistent with being targets of the pathway. Genetic interactions with Egfr further linked two of the genes, Sulfated (Sulf1), an endosulfatase gene, and CG4096, an A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS) gene, to the pathway. Sulf1 showed a strong genetic interaction with the neuregulin-like ligand vein (vn) and may influence binding of Vn to heparan-sulfated proteoglycans (HSPGs). How Drosophila Egfr activity is modulated by CG4096 is unknown, but interestingly vertebrate EGF ligands are regulated by a related ADAMTS protein. We suggest Sulf1 and CG4096 are negative feedback regulators of Egfr signaling that function in the extracellular space to influence ligand activity.

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Section: Discussionmentioning

confidence: 99%

New Negative Feedback Regulators of Egfr Signaling inDrosophila

et al. 2012

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“…Based on sequence analysis, ADAMTS15 contains three potential N -linked glycosylation sites [201]. Molokwu et al have recently reported a potential cleavage within the disintegrin domain resulting in the release of a C -terminal fragment approximately 53 kDa in size [202]. …”

Section: Adamts15mentioning

confidence: 99%

“…ADAMTS15 was found to contain one androgen response element (ARE) in its promoter and 12 ARE’s within the gene itself using NUBIscan online nuclear receptor binding site search tool. Stimulation of an androgen responsive cell line LnCAP with dihydrotestosterone resulted in marked reduction in ADAMTS15 expression levels [202]. …”

Section: Adamts15mentioning

confidence: 99%

Emerging Roles of ADAMTSs in Angiogenesis and Cancer

Kumar

Rao

2012

Cancers

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A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs—ADAMTSs—are a multi-domain, secreted, extracellular zinc metalloproteinase family with 19 members in humans. These extracellular metalloproteinases are known to cleave a wide range of substrates in the extracellular matrix. They have been implicated in various physiological processes, such as extracellular matrix turnover, melanoblast development, interdigital web regression, blood coagulation, ovulation, etc. ADAMTSs are also critical in pathological processes such as arthritis, atherosclerosis, cancer, angiogenesis, wound healing, etc. In the past few years, there has been an explosion of reports concerning the role of ADAMTS family members in angiogenesis and cancer. To date, 10 out of the 19 members have been demonstrated to be involved in regulating angiogenesis and/or cancer. The mechanism involved in their regulation of angiogenesis or cancer differs among different members. Both angiogenesis-dependent and -independent regulation of cancer have been reported. This review summarizes our current understanding on the roles of ADAMTS in angiogenesis and cancer and highlights their implications in cancer therapeutic development.

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“…In addition, along with versican, it is also dysregulated in prostate cancer (24,25). To our knowledge, however, a knock-out mouse model for Adamts15 is currently unavailable, and its biology is poorly described.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, aberrant expression of ADAMTS15, along with versican (VCAN), is implicated in prostate cancer progression (24,25), whereas the accumulation of versican in breast, prostate, and ovarian tumors can promote metastasis (26 -28).…”

Section: Amentioning

confidence: 99%

Biosynthesis and Expression of a Disintegrin-like and Metalloproteinase Domain with Thrombospondin-1 Repeats-15

Dancevic¹,

Fraser²,

Smith

et al. 2013

Journal of Biological Chemistry

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Background: ADAMTS proteoglycanases show proteolytic activity toward versican and other proteoglycans. Results: ADAMTS15, which cleaves versican, is expressed during early cardiac development and during musculoskeletal development. Conclusion: With unique and overlapping biological properties, ADAMTS15 is likely to have cooperative roles with other members of the ADAMTS proteoglycanase clade. Significance: Versican cleavage has profound effects on developmental morphogenesis and regulates cancer cell behavior.

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Androgen RegulatesADAMTS15Gene Expression in Prostate Cancer Cells

Cited by 17 publications

References 52 publications

New Negative Feedback Regulators of Egfr Signaling inDrosophila

New Negative Feedback Regulators of Egfr Signaling inDrosophila

Emerging Roles of ADAMTSs in Angiogenesis and Cancer

Biosynthesis and Expression of a Disintegrin-like and Metalloproteinase Domain with Thrombospondin-1 Repeats-15

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