Inhibin/activin and ovarian cancer.

2004 ◽  
Vol 11 (1) ◽  
pp. 35-49 ◽  
Author(s):  
D M Robertson ◽  
H G Burger ◽  
P J Fuller
Keyword(s):  
Ovarian Cancer ◽  
Granulosa Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Alpha Subunit ◽  
Beta Subunits ◽  
Granulosa Cell Tumours

Inhibin and activin are members of the transforming growth factor beta (TGFbeta) family of cytokines produced by the gonads, with a recognised role in regulating pituitary FSH secretion. Inhibin consists of two homologous subunits, alpha and either betaA or betaB (inhibin A and B). Activins are hetero- or homodimers of the beta-subunits. Inhibin and free alpha subunit are known products of two ovarian tumours (granulosa cell tumours and mucinous carcinomas). This observation has provided the basis for the development of a serum diagnostic test to monitor the occurrence and treatment of these cancers. Transgenic mice with an inhibin alpha subunit gene deletion develop stromal/granulosa cell tumours suggesting that the alpha subunit is a tumour suppressor gene. The role of inhibin and activin is reviewed in ovarian cancer both as a measure of proven clinical utility in diagnosis and management and also as a factor in the pathogenesis of these tumours. In order to place these findings into perspective the biology of inhibin/activin and of other members of the TGFbeta superfamily is also discussed.

scholarly journals The role of inhibins and activins in prostate cancer pathogenesis.

2000 ◽  
pp. 243-256 ◽  
Author(s):  
C R Dowling ◽  
G P Risbridger
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Prostate Gland ◽  
Prostate Carcinogenesis ◽  
Cancer Pathogenesis ◽  
Number Of Patients ◽  
Related Proteins

Successful prostate cancer diagnosis and management continue to provide challenges for the clinician. While interventions aimed at the containment of both early and late disease continue to fail in a significant number of patients, the search for answers must incorporate an analysis of the processes of normal and aberrant growth and development within the gland itself. Inhibin and its structurally related protein, activin, are members of the transforming-growth-factor beta (TGFbeta) superfamily. Originally identified as regulators of FSH, these proteins are now recognised to have widespread biological functions. This might be expected of proteins that are structurally homologous to TGFbeta itself, which is recognised to have regulatory roles in both normal and malignant prostate tissue. The aim of this review is to examine the relationship between inhibins, activins and their related proteins and the development of prostate cancer. The homology with TGF, the pluripotent effects of activin on various tissues and the roles for inhibins in ovarian cancer make activins and inhibins candidate growth factors for involvement at multiple sites in the progression from benign disease to cancer. In compiling this review, we aim to delineate the changes in inhibins and activins in this pathway and in doing so implicate their potential roles in the progression of carcinogenesis. We will compare the changes in inhibin and its related proteins in prostate cancer to those that are known in ovarian cancer. We will discuss the similarities and differences between the putative role of activins and TGFbeta in prostate carcinogenesis. The importance of this review lies in demonstrating that inhibin, an endocrine hormone, and its related proteins may contribute to endocrine-related cancers, such as that of the prostate gland.

Smad4/DPC4

2018 ◽  
Vol 71 (8) ◽  
pp. 661-664 ◽  
Author(s):  
Aoife J McCarthy ◽  
Runjan Chetty
Keyword(s):  
Pancreatic Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Intraepithelial Neoplasia ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Signal Transduction Proteins ◽  
Prostate Cancers

Smad4 or DPC4 belongs to a family of signal transduction proteins that are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor beta (TGF-β) signaling via several pathways. The gene acts as a tumour suppressor gene and inactivation of smad4/DPC4 is best recognised in pancreatic cancer. However, smad4/DPC4 is also mutated in other conditions and cancers such as juvenile polyposis syndrome with and without hereditary haemorrhagic telangiectasia, colorectal and prostate cancers.Immunohistochemistry for smad4/DPC4 protein is most useful in separating benign/reactive conditions from pancreatic cancer in needle/core biopsies. In normal and reactive states, the protein is localised to the cytoplasm and nucleus, while the protein is lost in high-grade pancreatic intraepithelial neoplasia/carcinoma in situ and pancreatic cancer.

FOXL2 in adult‐type granulosa cell tumour of the ovary: oncogene or tumour suppressor gene?

2021 ◽  
Author(s):  
Jessica A. Pilsworth ◽  
Anne‐Laure Todeschini ◽  
Samantha J. Neilson ◽  
Dawn R. Cochrane ◽  
Daniel Lai ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Cell Tumour ◽  
Granulosa Cell Tumour ◽  
Adult Type

scholarly journals Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jayarami Reddy Medapati ◽  
Deepthi Rapaka ◽  
Veera Raghavulu Bitra ◽  
Santhosh Kumar Ranajit ◽  
Girija Sankar Guntuku ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Morphological Changes ◽  
Serum Levels ◽  
Cb1 Receptors ◽  
Protective Effects ◽  
Renal Hypertrophy ◽  
Necrosis Factor Alpha

Abstract Background The endocannabinoid CB1 receptor is known to have protective effects in kidney disease. The aim of the present study is to evaluate the potential agonistic and antagonistic actions and to determine the renoprotective potential of CB1 receptors in diabetic nephropathy. The present work investigates the possible role of CB1 receptors in the pathogenesis of diabetes-induced nephropathy. Streptozotocin (STZ) (55 mg/kg, i.p., once) is administered to uninephrectomised rats for induction of experimental diabetes mellitus. The CB1 agonist (oleamide) and CB1 antagonist (AM6545) treatment were initiated in diabetic rats after 1 week of STZ administration and were given for 24 weeks. Results The progress in diabetic nephropathy is estimated biochemically by measuring serum creatinine (1.28±0.03) (p < 0.005), blood urea nitrogen (67.6± 2.10) (p < 0.001), urinary microprotein (74.62± 3.47) (p < 0.005) and urinary albuminuria (28.31±1.17) (p < 0.0001). Renal inflammation was assessed by estimating serum levels of tumor necrosis factor alpha (75.69±1.51) (p < 0.001) and transforming growth factor beta (8.73±0.31) (p < 0.001). Renal morphological changes were assessed by estimating renal hypertrophy (7.38± 0.26) (p < 0.005) and renal collagen content (10.42± 0.48) (p < 0.001). Conclusions From the above findings, it can be said that diabetes-induced nephropathy may be associated with overexpression of CB1 receptors and blockade of CB1 receptors might be beneficial in ameliorating the diabetes-induced nephropathy. Graphical abstract

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