Insensitivity to the growth inhibitory effects of activin A: An acquired capability in prostate cancer progression

Ottley, Edward; Gold, Elspeth

doi:10.1016/j.cytogfr.2012.04.004

Cited by 16 publications

(15 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other proposed mechanisms for the development of resistance by tumour cells to the growth inhibitory effects of activin-A include up-regulation of follistatin [60, 61]. Our results showed significantly higher concentrations of follistatin at the gene and protein levels that positively correlated with the progression of colon cancer in the used model.…”

Section: Discussionsupporting

confidence: 54%

Activins and their related proteins in colon carcinogenesis: insights from early and advanced azoxymethane rat models of colon cancer

Refaat

El-Shemi

et al. 2016

BMC Cancer

View full text Add to dashboard Cite

BackgroundActivin-A may exert pro- or anti-tumorigenic activities depending on cellular context. However, little is known about its role, or the other mature activin proteins, in colorectal carcinoma (CRC). This study measured the expression of activin βA- & βB-subunits, activin type IIA & IIB receptors, smads 2/3/4/6/7 and follistatin in CRC induced by azoxymethane (AOM) in rats. The results were compared with controls and disseminated according to the characteristics of histopathological lesions.MethodsEighty male Wistar rats were allocated into 20 controls and the remaining were equally divided between short ‘S-AOM’ (15 weeks) and long ‘L-AOM’ (35 weeks) groups following injecting AOM for 2 weeks. Subsequent to gross and histopathological examinations and digital image analysis, the expression of all molecules was measured by immunohistochemistry and quantitative RT-PCR. Activin-A, activin-B, activin-AB and follistatin were measured by ELISA in serum and colon tissue homogenates.ResultsColonic pre-neoplastic and cancerous lesions were identified in both AOM groups and their numbers and sizes were significantly (P < 0.05) greater in the L-AOM group. All the molecules were expressed in normal colonic epithelial cells. There was a significantly (P < 0.05) greater expression of βA-subunit, IIB receptor and follistatin in both pre-neoplastic and cancerous tissues. Oppositely, a significant (P < 0.05) decrease in the remaining molecules was detected in both AOM groups. Metastatic lesions were only observed within the L-AOM group and were associated with the most significant alterations of all molecules. Significantly higher concentrations of activin-A and follistatin and lower activin-AB were also detected in both groups of AOM. Tissue and serum concentrations of activin-A and follistatin correlated positively, while tissue activin-AB inversely, and significantly with the numbers and sizes of colonic lesions.ConclusionsNormal rat colon epithelial cells are capable of synthesising, controlling as well as responding to activins in a paracrine/autocrine manner. Colonic activin systems are pathologically altered during tumorigenesis and appear to be time and lesion-dependent. Activins could also be potential sensitive markers and/or molecular targets for the diagnosis and/or treatment of CRC. Further studies are required to illustrate the clinical value of activins and their related proteins in colon cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2914-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 54%

Activins and their related proteins in colon carcinogenesis: insights from early and advanced azoxymethane rat models of colon cancer

Refaat

El-Shemi

et al. 2016

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Interestingly, circulating levels of activin-A were demonstrated to increase significantly in metastatic prostate and breast cancers. 41,42 In addition, SMAD deletions are observed only in 1–2% of breast cancers. 40 In other words, this signaling pathway remains intact in most of the breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Activin-A signaling promotes epithelial–mesenchymal transition, invasion, and metastatic growth of breast cancer

et al. 2015

View full text Add to dashboard Cite

Background:Activins belong to the transforming growth factor-β (TGF-β) superfamily of cytokines. Although the role of TGF-β in cancer progression has been highly advocated, the role of activin signaling in cancer is not well known. However, overexpression of activin-A has been observed in several cancers.Aims:The gene expression profile indicated higher expression of Activin-A in breast tumors. Hence the aim of this study was to evaluate the status and role of Activin signaling pathway in these tumors.Methods:Microarray analysis was performed to reveal gene expression changes in breast tumors. The results were validated by quantitative PCR and immunohistochemical analysis in two independent sets of normal and tumor samples. Further, correlation of activin expression with survival and distant metastasis was performed to evaluate its possible role in tumor progression. We used recombinant activin-A, inhibitors, overexpression, and knockdown strategies both in vitro and in vivo, to understand the mechanism underlying the protumorigenic role of this signaling pathway.Results:We report that activin-A signaling is hyperactivated in breast cancers as indicated by higher activin-A, phosphoSMAD2, and phosphoSMAD3 levels in advanced breast cancers. Bone morphogenetic proteins and molecules involved in this signaling pathway were downregulated, suggesting its suppression in breast cancers. Activin-A expression correlates inversely with survival and metastasis in advanced breast cancers. Further, activin-A promotes anchorage-independent growth, epithelial–mesenchymal transition, invasion, angiogenesis, and stemness of breast cancer cells. We show that activin-A-induced phenotype is mediated by SMAD signaling pathway. In addition, activin-A expression affects the tumor-forming ability and metastatic colonization of cancer cells in nude mice.Conclusions:These results suggest that activin-A has a critical role in breast cancer progression and, hence, targeting this pathway can be a valuable strategy in treating breast cancer patients.

show abstract

“…The functions of activin appear to differ between species and tissue type and alterations in activin signalling have been implicated in the development of a variety of cancers including prostate, breast and gonadal tumours . Activin A can inhibit cell proliferation in the low-to medium-grade human prostate cancer cell lines LNCaP and DU145 while the more advanced grade PC3 cells are insensitive to activin A (Ottley and Gold, 2012). In contrast, lung cancer cell lines treated with activin A increased proliferation (Seder et al, 2009).…”

Section: Introductionmentioning

confidence: 97%

Activins and activin antagonists in the human ovary and ovarian cancer

Reader

Gold

2015

Molecular and Cellular Endocrinology

Self Cite

View full text Add to dashboard Cite

Insensitivity to the growth inhibitory effects of activin A: An acquired capability in prostate cancer progression

Cited by 16 publications

References 70 publications

Activins and their related proteins in colon carcinogenesis: insights from early and advanced azoxymethane rat models of colon cancer

Activins and their related proteins in colon carcinogenesis: insights from early and advanced azoxymethane rat models of colon cancer

Activin-A signaling promotes epithelial–mesenchymal transition, invasion, and metastatic growth of breast cancer

Activins and activin antagonists in the human ovary and ovarian cancer

Contact Info

Product

Resources

About