Dataset Information

CDKN2A (p16INK4A) affects the anti?tumor effect of CDK inhibitor in somatotroph adenomas.

ABSTRACT: The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study was to investigate the pathological role of the INK4 family and evaluate the effectiveness of CDK4 inhibitor, palbociclib, in somatotroph adenoma. RNA?Seq, RT?PCR, and immunohistochemistry were applied to measure the levels and correlations of the INK4 family with angiogenesis, CDKs, EMT, and therapeutic targets. MTS, flow cytometry, and ELISA were used to investigate the bio?activity in GH3 and GT1?1 cell lines after palbociclib treatment. Compared with lactotroph adenoma, gonadotroph adenoma, and corticotroph adenoma, somatotroph samples demonstrated higher expression of CDKN2A and SSTR2 but a lower expression of EGFR, CDK4, and CDH2 (P<0.05). CDKN2A positively correlates with SSTR2, and negatively with CDK4, EGFR, and CDH2. Patients with lower CDKN2A had larger tumor size (P=0.016) and more invasive potential (P=0.023). Palbociclib inhibited cell proliferation, induced G1 phase arrest, reduced GH/IGF?1 secretion of GH3 and GT1?1 cell lines (P<0.05), and had a more prominent role in GH3 cells (P<0.05). CDKN2A inhibited the bio?activity by modulating CDK4, and high CDKN2A predicted the insensitivity to CDK4 inhibitor, palbociclib, in somatotroph adenoma patients. In summary, the present study shows CDKN2A inhibited the bio?activity by modulating CDK4, and high CDKN2A predicts the insensitivity to CDK4 inhibitor, Palbociclib, in somatotroph adenoma patients.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7797444 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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CDKN2A (p16INK4A) affects the anti‑tumor effect of CDK inhibitor in somatotroph adenomas.

Chen Yiyuan Y Li Zhenye Z Fang Qiuyue Q Wang Hongyun H Li Chuzhong C Gao Hua H Zhang Yazhuo Y

International journal of molecular medicine 20201202 2

The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study was to investigate the pathological role of the INK4 family and evaluate the effectiveness of CDK4 inhibitor, palbociclib, in somatotroph adenoma. RNA‑Seq, RT‑PCR, and immunohistochemistry were applied to measure the levels and correlations of the INK4 family with angiogenesis, CDKs, EMT, and therapeutic targets. MTS, flow cytom ...[more]

PMID: 33416096

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Project description:Studies have revealed that genetic and functional aberrations of oncogenes, tumor?suppressor genes, signaling pathways and receptors are among the most prominent events in pituitary tumorigenesis, and a potent biomarker would be helpful for early diagnosis, subsequent treatment and disease control. The present study investigated the expression signatures of solute carrier family 20 member 1, also known as phosphate transporter 1 (SLC20A1) and the Wnt/??catenin signaling pathway in 52 patients with somatotroph adenomas. According to immunohistochemistry analysis, the H?score of SLC20A1 was 222.6±15.2 in invasive tumor samples and 144.5±30.4 in non?invasive tumor samples (P<0.01), while the H?scores of ??catenin were 210.1±21.4 and 134.9±32.7, respectively (P<0.05). The H?scores of Wnt inhibitory factor 1 (Wif1) exhibited the opposite trend, with scores of 134.5±22.7 and 253.6±14.8, respectively (P<0.01). The H?scores of SLC20A1 were negatively associated with those of Wif1 in somatotroph adenomas (correlation coefficient r=?0.367). The mean progression?free survival in the low SLC20A1 group was longer than that in the group with high SLC20A1 H?scores (P=0.024). Reverse transcription?quantitative PCR (RT?qPCR) and western blotting confirmed the interference efficiency of the segments short hairpin (Sh)?B?SLC20A1 and Sh?C?SLC20A1. Cell proliferation experiments revealed that the cell viability of the Sh?B?SLC20A1 group was 76.3±4.5, 65.7±3.7 and 53.1±3.2% of that of control GH3 cells after 24, 48 and 72 h of transfection, respectively, while the cell viability of the Sh?C?SLC20A1 group was 86.4±5.7, 75.6±4.4 and 67.5±3.8%, respectively (P<0.05). ELISA analysis demonstrated the growth hormone (GH) levels in the Sh?B?SLC20A1 and Sh?C?SLC20A1 groups to be 34.7±10.4 and 54.6±14.4%, respectively, of that of control GH3 cells (P<0.05). The transmembrane invasion assay revealed that knocking down SLC20A1 signi?cantly suppressed cell invasion in the Sh?B?SLC20A1 and Sh?C?SLC20A1 groups. RT?qPCR and western blotting demonstrated that Sh?B?SLC20A1 and Sh?C?SLC20A1 evidently increased the levels of Wif1 and secreted frizzled?related protein 4. The present data suggested that SLC20A1 levels are positively associated with tumor size, invasive behavior and tumor recurrence in somatotroph adenomas. Furthermore, SLC20A1 may be associated with the activation of the Wnt/??catenin signaling pathway.

Dataset Information

CDKN2A (p16INK4A) affects the anti?tumor effect of CDK inhibitor in somatotroph adenomas.

Publications

CDKN2A (p16INK4A) affects the anti‑tumor effect of CDK inhibitor in somatotroph adenomas.

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