Prostate cancer and acromegaly

Corrêa, Lívia L.; Lima, Giovanna Aparecida Balarini; Paiva, Helena Borges; Silva, Cíntia M. dos Santos; Cavallieri, Suzana Aquino; Miranda, Luiz Carlos; Gadelha, Mônica R.

doi:10.1590/s0004-27302009000800009

Cited by 18 publications

(10 citation statements)

References 56 publications

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“…The precise role(s) of these canonical GH response cis-elements in GH-dependent increase in ZEB2-NAT expression remains to be defined. In addition to the glomerular podocyte, our finding of GH-dependent increase in ZEB2 expression is also relevant to the role of GH in malignancies such as breast and prostate cancer wherein the GH/GHR axis has been demonstrated to play a permissive role (35). It is noteworthy that we were unable to verify expression of a closely related member of the ZEB family of protein, ZEB1 (␦EF1/ZFHX1A), in the podocyte (data not shown).…”

Section: Discussionmentioning

confidence: 74%

Growth Hormone (GH)-dependent Expression of a Natural Antisense Transcript Induces Zinc Finger E-box-binding Homeobox 2 (ZEB2) in the Glomerular Podocyte

Kumar

Kotlyarevska

Dejkhmaron

et al. 2010

Journal of Biological Chemistry

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Growth hormone (GH) excess results in structural and functional changes in the kidney and is implicated as a causative factor in the development of diabetic nephropathy (DN). Glomerular podocytes are the major barrier to the filtration of serum proteins, and altered podocyte function and/or reduced podocyte number is a key event in the pathogenesis of DN. We have previously shown that podocytes are a target for GH action. To elucidate the molecular basis for the effects of GH on the podocyte, we conducted microarray and RT-quantitative PCR analyses of immortalized human podocytes and identified zinc finger E-box-binding homeobox 2 (ZEB2) to be up-regulated in a GH dose-and time-dependent manner. We established that the GH-dependent increase in ZEB2 levels is associated with increased transcription of a ZEB2 natural antisense transcript required for efficient translation of the ZEB2 transcript. GH down-regulated expression of E-and P-cadherins, targets of ZEB2, and inhibited E-cadherin promoter activity. Mutation of ZEB2 binding sites on the E-cadherin promoter abolished this effect of GH on the E-cadherin promoter. Whereas GH increased podocyte permeability to albumin in a paracellular albumin influx assay, shRNA-mediated knockdown of ZEB2 expression abrogated this effect. We conclude that GH increases expression of ZEB2 in part by increasing expression of a ZEB2 natural antisense transcript. GH-dependent increase in ZEB2 expression results in loss of P-and E-cadherins in podocytes and increased podocyte permeability to albumin. Decreased expression of P-and E-cadherins is implicated in podocyte dysfunction and epithelial-mesenchymal transition observed in DN. We speculate that the actions of GH on ZEB2 and P-and E-cadherin expression play a role in the pathogenesis of microalbuminuria of DN. Pituitary growth hormone (GH)5 is essential for postnatal growth in mammals. In addition to growth, GH affects the metabolism of fat, protein, and carbohydrate (1). GH exerts these actions both by its direct effect on target organs and by stimulating the production of insulin-like growth factor-1 (IGF-1). At the tissue level, these pleiotropic actions of GH result from the interaction of GH with a specific cell surface receptor, the GH receptor (GHR). Whereas the GHR is ubiquitously expressed, the role and effects of GH have been most intensely investigated in organs and tissues such as liver, bone, muscle, and adipocytes in which GHR expression is substantial and are thus considered canonical targets of GH action. However, recent reports have highlighted the biological effects and physiological relevance of GH action in non-canonical targets such as the blastocyst (2), colonic epithelial cells (3), cardiomyocytes (4), and neurons (5).GH excess in both the human (acromegaly) and in transgenic animal models is characterized by significant structural and functional changes in the kidney (6 -8). An overactive GH/ GHR axis is implicated as a causative factor in the development of diabetic nephropathy (9 -11). Our previous study...

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Section: Discussionmentioning

confidence: 74%

Growth Hormone (GH)-dependent Expression of a Natural Antisense Transcript Induces Zinc Finger E-box-binding Homeobox 2 (ZEB2) in the Glomerular Podocyte

Kumar

Kotlyarevska

Dejkhmaron

et al. 2010

Journal of Biological Chemistry

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“…The correlation between acromegaly and prostate cancer, until the present moment, is circumstantial. However, there is a correlation between serum levels of IGF-I at the upper limit of normality and prostrate cancer in the overall population (8,9).…”

Section: Introductionmentioning

confidence: 99%

Frequency of various types of neoplasia in a group of acromegalic patients

Bolfi

Miot

Resende

et al. 2013

Arq Bras Endocrinol Metab

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Objective: To determine the frequency of colon cancer, primary hyperparathyroidism, thyroid tumor, and skin cancer in all acromegalic patients in follow-up at the Clinics Hospital -Botucatu Medical School, from 2005 to 2011. Subjects and methods: These patients were evaluated retrospectively for colon cancer, primary hyperparathyroidism, dermatological, and thyroid tumors. Results: Of 29 patients included at the beginning of the study, two were excluded. Among 19 patients submitted to colonoscopy, one presented colon adenocarcinoma (5%). Thyroid nodules were present in 63% of patients, and papilliferous carcinoma was confirmed in two patients (7,7%). Four patients were confirmed as having primary hyperparathyroidism (15%). The most common dermatologic lesions were thickened skin (100%), acrochordons (64%), epidermal cysts (50%), and pseudo-acanthosis nigricans Dentre os 19 pacientes submetidos à colonoscopia, um apresentou adenocarcinoma de cólon (5%). Nódulos de tireoide estiveram presentes em 65% dos pacientes e carcinoma papilífero, em dois deles (7,7%). Quatro pacientes apresentaram hiperparatireoidismo primário (15%). A maioria das lesões de pele foram: espessamento (100%), acrochordons (64%), cistos epidérmicos (50%), pseudoacantose nigricans (50%) e apenas um paciente apresentou carcinoma basocelular. Conclusão: O tamanho da amostra é pequeno, mas nossos achados confirmam a alta frequência da neoplasia da tireoide e hiperparatireroidismo neste grupo de pacientes. Arq Bras Endocrinol Metab. 2013;57(8):612-6 Descritores

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“…This is a member of the kallikrein family of serine protease [31] and it is assumed that rising PSA levels during the natural history of PCa enhances the disease progression by proteolytically cleaving IGFBP-3, thereby increasing the amount of bioavailable IGF-1. [32] Previous study on Arab males indicated that IGF-1 and IGFBP-3 reached their peak levels during adolescence and gradually lowered with age. [33] IGFBP-3, the most prevalent form of the IGFBPs, has been linked with prostatic growth.…”

Section: Discussionmentioning

confidence: 99%

Combination of insulin-like growth factor-1, IGF binding protein-3, chromogranin A and prostate specific antigen can improve the detection of prostate cancer

Saleh¹,

Adly²,

Nassir³

2017

JCMT

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Aim: Prostate cancer (PCa) is the second most prevalent male cancer worldwide and designated the sixth most frequent male cancer in Arab countries. Although prostate specific antigen (PSA) has become the best and most valuable biomarker for screening of PCa, elevated levels of PSA can reflect the presence of malignant cells but can overlap with benign prostatic diseases. There is a necessity to develop and improve current tools for early detection and diagnosis of PCa. This study was done to evaluate the validation of serum insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), chromogranin A (CgA) and combination with PSA in treatment of benign prostatic hyperplasia (BPH) and PCa patients. Methods: The study included 72 patients with PCa, 70 BPH patients and 56 healthy male subjects of matched age. Full history and clinical data were recorded for all subjects. Results: Serum PSA attained sensitivity of 84% at 82% specificity with an accuracy of 83%, although IGF-1, IGFBP-3 and CgA did not recognize PCa patients. Conclusion: Combinations of IGF-1 and IGFBP-3 biomarkers with PSA were effectively differentiated between PCa and control groups as well as improving the overall value of sensitivity, specificity and diagnostic accuracy of PCa to 85% and 86% for IGF-1/PSA and IGFP-3/PSA respectively. Key words:Prostate cancer, benign prostatic hyperplasia, insulin-like growth factor-1, IGF binding protein-3, chromogranin A ABSTRACTArticle history:

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Prostate cancer and acromegaly

Cited by 18 publications

References 56 publications

Growth Hormone (GH)-dependent Expression of a Natural Antisense Transcript Induces Zinc Finger E-box-binding Homeobox 2 (ZEB2) in the Glomerular Podocyte

Growth Hormone (GH)-dependent Expression of a Natural Antisense Transcript Induces Zinc Finger E-box-binding Homeobox 2 (ZEB2) in the Glomerular Podocyte

Frequency of various types of neoplasia in a group of acromegalic patients

Combination of insulin-like growth factor-1, IGF binding protein-3, chromogranin A and prostate specific antigen can improve the detection of prostate cancer

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