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Overexpression of activin A in stage IV colorectal cancer.

ABSTRACT: Activins and inhibins are dimeric polypeptides that belong to the transforming growth factor beta (TGF-beta) superfamily and that bind to transmembrane receptors with serine/threonine kinase activity. The aim of this study was to characterise, in colon cancer cell lines and in normal and malignant human colon tissues, levels of expression of inhibin subunits that are involved in activin/inhibin dimer formation, and of the type I and II activin receptors (actRI and actRII).Expression of inhibin subunits and activin receptors was analysed by northern blot analysis. Inhibin betaA and activin receptor expression were also assessed by use of polymerase chain reaction (PCR). In addition, activin A/inhibin betaA localisation in human colon samples was assessed by immunohistochemistry and in situ hybridisation.Inhibin betaA mRNA was expressed in CaCo2 cells but not in SW 837 or SW 1463 cells whereas inhibin betaB and inhibin alpha were below the level of detection. In contrast, all four activin receptors were present in the three cell lines. Colon cancers overexpressed inhibin betaA mRNA in comparison with normal colon, and this overexpression was greatest in stage IV tumours. ActRIb mRNA levels were slightly higher in the normal colon than in cancer tissues. By immunohistochemistry and in situ hybridisation, activin A and inhibin betaA mRNA were present in the mucosal epithelial cells in normal tissues from patients with stage I disease but were either absent or weakly present in normal tissues from patients with stage IV disease. Conversely, they were present at weak to moderate levels in stage I cancers but at high levels in stage IV cancers.Our findings indicate that activin A is overexpressed in human colorectal tumours, especially in stage IV disease, raising the possibility that activin A may have a role in advanced colorectal cancer.

SUBMITTER: Wildi S

PROVIDER: S-EPMC1728425 | biostudies-other | 2001 Sep

REPOSITORIES: biostudies-other

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Overexpression of activin A in stage IV colorectal cancer.

Wildi S S Kleeff J J Maruyama H H Maurer C A CA Büchler M W MW Korc M M

Gut 20010901 3

<h4>Background and aims</h4>Activins and inhibins are dimeric polypeptides that belong to the transforming growth factor beta (TGF-beta) superfamily and that bind to transmembrane receptors with serine/threonine kinase activity. The aim of this study was to characterise, in colon cancer cell lines and in normal and malignant human colon tissues, levels of expression of inhibin subunits that are involved in activin/inhibin dimer formation, and of the type I and II activin receptors (actRI and act ...[more]

PMID: 11511564

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Project description:ImportanceThe potential relationship between obesity and colorectal cancer (CRC) outcome is poorly understood in patients with late-stage disease. Increased body mass index may negate aspirin use for cancer prevention, but its role as a factor on the effectiveness of postdiagnosis aspirin use is unclear.ObjectiveTo evaluate how prediagnosis obesity and postdiagnosis aspirin use may be associated with overall survival in patients with late-stage colorectal cancer.Design, setting, and participantsThis cross-sectional study used self-reported data from patients with metastatic or treatment-refractory disease who consented to a clinical protocol at MD Anderson Cancer Center, a large US cancer treatment center. Patients were enrolled between 2010 and 2018 and followed up for mortality through July 2020. Analyses were conducted through March 2022.ExposuresBody mass index in the decade prior to initial diagnosis and regular aspirin use at survey completion.Main outcomes and measuresOverall survival was measured from stage IV diagnosis until death or last follow-up. Cox proportional hazards models were constructed to estimate associations of prediagnosis obesity and postdiagnosis aspirin use with overall survival.ResultsOf 656 patients included in this analysis, 280 (42.7%) were women, 135 (20.6%) were diagnosed with CRC before age 45 years, 414 (63.1%) were diagnosed between ages 45 and 65 years, and 107 (16.3%) were diagnosed at 65 years or older; 105 patients (16.0%) were Black or Hispanic, and 501 (76.4%) were non-Hispanic White. Controlling for age, sex, race, stage at initial diagnosis, and weight change between prediagnosis and survey date, patients with obesity in the decade prior to CRC diagnosis had significantly higher likelihood of death (hazard ratio, 1.45; 95% CI, 1.11-1.91) compared with those with normal prediagnosis body mass index. Furthermore, only patients with normal prediagnosis body mass index experienced significant survival benefit with postdiagnosis aspirin use (hazard ratio, 0.59; 95% CI, 0.39-0.90).Conclusions and relevanceIn this cross-sectional study, our findings suggest potentially differential tumor development in the long-term physiologic host environment of obesity. Confirmation and further evaluation are needed to determine whether prediagnosis body mass index may be used to estimate the benefit from postdiagnosis aspirin use.

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Overexpression of activin A in stage IV colorectal cancer.

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Overexpression of activin A in stage IV colorectal cancer.

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