Growth hormone (GH) is important for cell growth and differentiation, has multiple effects on lymphoid tissue and may promote blast cell proliferation and cancer development. We studied the effect of GH on longevity and tumour formation in Atm-deficient mice, an established model of the human cancer prone syndrome ataxia telangiectasia (AT). AT is a devastating recessive disorder that is characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability and cancer susceptibility. Since AT patients also show endocrinological abnormalities the question has been raised as to whether GH therapy could be beneficial and/or increase the cancer risk in AT. We found that treatment with GH significantly increased longevity of Atm-deficient mice. In addition, GH ameliorated locomotoric behaviour and improved T-cell immunity. Thus, our data demonstrated that GH treatment is not necessarily accompanied by increased cancer development in diseases with chromosomal instability and cancer susceptibility and might be beneficial for AT patients.

Download full-text PDF

Source
http://dx.doi.org/10.1080/08977190903112663DOI Listing

Publication Analysis

Top Keywords

atm-deficient mice
12
growth hormone
8
cancer development
8
chromosomal instability
8
instability cancer
8
cancer susceptibility
8
cancer
6
hormone supplementation
4
supplementation increased
4
increased latency
4

Similar Publications

The cGAS-STING, p38 MAPK, and p53 pathways link genome instability to accelerated cellular senescence in ATM-deficient murine lung fibroblasts.

Proc Natl Acad Sci U S A

January 2025

Department of Human Molecular Genetics and Biochemistry, Faculty of Health & Medical Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

Ataxia-telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of the homeostatic protein kinase ATM. The complex phenotype of A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts from A-T patients exhibit premature senescence, highlighting the association between genome instability, cellular senescence, and aging.

View Article and Find Full Text PDF
Article Synopsis
  • * The study reveals that most ATM-deficient T-LBL cultures have various genomic alterations in the PTEN gene, resulting in the absence of functional PTEN protein and constant activation of AKT signaling.
  • * These lymphomas are sensitive to the AKT inhibitor MK-2206, indicating they rely on pAKT signaling for survival, and this loss of PTEN expression and activation of AKT is not seen in non-cancerous thymocytes.
View Article and Find Full Text PDF

Background: Ataxia-telangiectasia (A-T) is a rare autosomal recessive multi-system and life-shortening disease, characterized by progressive cerebellar neurodegeneration, immunodeficiency, radiation sensitivity and cancer predisposition, with high incidence of leukemia and lymphoma. A-T is caused by mutations in the gene encoding for ATM protein that has a major role in maintaining the integrity of the genome. Because there are no cures for A-T, we aimed to tackle immunodeficiency and prevent cancer onset/progression by transplantation therapy.

View Article and Find Full Text PDF

Accumulating evidence supports the concept that DNA damage response targeted therapies can improve antitumor immune response by increasing the immunogenicity of tumor cells and improving the tumor immune microenvironment. Ataxia telangiectasia mutated (ATM) is a core component of the DNA repair system. Although the ATM gene has a significant mutation rate in many human cancers, including colorectal, prostate, lung, and breast, it remains understudied compared with other DDR-involved molecules such as PARP and ATR.

View Article and Find Full Text PDF

Inhibitors of DNA-dependent protein kinase (PRKDC; DNA-PK) sensitize cancers to radiotherapy and DNA-damaging chemotherapies, with candidates in clinical trials. However, the degree to which DNA-PK inhibitors also sensitize normal tissues remains poorly characterized. In this study, we compare tumor growth control and normal tissue sensitization following DNA-PK inhibitors in combination with radiation and etoposide.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!