Endocrine-related cancer最新文献

Cushing syndrome from an ACTH-producing pheochromocytoma or paraganglioma: structured review of 94 cases 由分泌促肾上腺皮质激素的嗜铬细胞瘤或副神经节瘤引发的库欣综合征：94 个病例的结构性回顾

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2024-09-01 DOI: 10.1530/erc-24-0029

David Kishlyansky, Alexander A Leung, Janice Pasieka, Amita Mahajan, Gregory Kline

{"title":"Cushing syndrome from an ACTH-producing pheochromocytoma or paraganglioma: structured review of 94 cases","authors":"David Kishlyansky, Alexander A Leung, Janice Pasieka, Amita Mahajan, Gregory Kline","doi":"10.1530/erc-24-0029","DOIUrl":"https://doi.org/10.1530/erc-24-0029","url":null,"abstract":"Adrenocorticotropic hormone-producing pheochromocytoma/paraganglioma are rare neuroendocrine tumours that co-secrete excess catecholamines and adrenocorticotropic hormone, resulting in Cushing syndrome. This review aims to summarize important patient characteristics, investigations, and outcomes in all cases reported in the English literature. A literature search was conducted to identify all English-language case reports and case-series describing adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas. Relevant characteristics were systematically recorded. Cases that did not provide definitive evidence of an ACTH-producing pheochromocytoma/paraganglioma were excluded. Our search strategy identified 93 published cases that met the inclusion criteria. We additionally reported one patient for a total of 94 cases. Details related to patient characteristics, laboratory data, and outcomes were commonly underreported. The median age was 47 years and females accounted for 72% of cases. A cushingoid appearance was reported in 82% and hypertension in 86%. Infections were reported in 23% of patients. Urinary metanephrines were elevated at least 3-fold above normal in 74%. ACTH levels were high in 88% and inappropriately normal in 12%. The median 24-hour urinary cortisol was 21-fold the upper limit of normal. Adrenalectomy was performed in nearly all patients with 88% achieving cure of both catecholamine and glucocorticoid excess. A total of 11 patients died. Metastases were uncommon (6%). Adrenocorticotropic hormone-producing pheochromocytoma/paraganglioma is associated with considerable morbidity and mortality. It should be considered in the diagnostic workup of all patients with ectopic Cushing Syndrome. Surgical cure is achieved in most patients and infections are the leading cause of peri-operative mortality.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPNMB promotes tumor growth and is a biomarker for lymphangioleiomyomatosis GPNMB 促进肿瘤生长，是淋巴管瘤病的生物标记物

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2024-04-01 DOI: 10.1530/erc-23-0312

Erin Gibbons, Manisha Taya, Huixing Wu, Samia H Lopa, Joel Moss, Elizabeth P. Henske, Francis X. Mccormack, Stephen R Hammes

{"title":"GPNMB promotes tumor growth and is a biomarker for lymphangioleiomyomatosis","authors":"Erin Gibbons, Manisha Taya, Huixing Wu, Samia H Lopa, Joel Moss, Elizabeth P. Henske, Francis X. Mccormack, Stephen R Hammes","doi":"10.1530/erc-23-0312","DOIUrl":"https://doi.org/10.1530/erc-23-0312","url":null,"abstract":"Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including glycoprotein non-metastatic melanoma protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB’s unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here we establish that GPNMB expression is dependent on mTORC1 signaling, and that GPNMB regulates TSC2-null tumor cell invasion in-vitro. Further, we demonstrate that GPNMB enhances TSC2-null xenograft tumor growth in-vivo, and that ectodomain release is required for this xenograft growth. We also show that GPNMB’s ectodomain is released from the cell surface of TSC2-null cells by proteases ADAM10 and 17, and we identify the protease target sequence on GPNMB. Finally, we demonstrate that GPNMB’s ectodomain is present at higher levels in LAM patient serum compared to healthy controls, and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Importance of 3β-hydroxysteroid dehydrogenases and their clinical use in prostate cancer 3β- 羟基类固醇脱氢酶的重要性及其在前列腺癌中的临床应用

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2024-04-01 DOI: 10.1530/erc-24-0023

Masaki Shiota, Satoshi Endo, Shigehiro Tsukahara, Tokiyosh Tanegashima, Satoshi Kobayashi, Takashi Matsumoto, Masatoshi Eto

{"title":"Importance of 3β-hydroxysteroid dehydrogenases and their clinical use in prostate cancer","authors":"Masaki Shiota, Satoshi Endo, Shigehiro Tsukahara, Tokiyosh Tanegashima, Satoshi Kobayashi, Takashi Matsumoto, Masatoshi Eto","doi":"10.1530/erc-24-0023","DOIUrl":"https://doi.org/10.1530/erc-24-0023","url":null,"abstract":"Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3β-hydroxysteroid dehydrogenases (3βHSDs) play critical roles in extragonadal androgen synthesis, especially 3βHSD1. Increased expression of 3βHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3βHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3βHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and post-transcriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3βHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3βHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuropilin-2 and soluble neuropilin-2 in neuroendocrine neoplasms 神经内分泌肿瘤中的神经肽-2 和可溶性神经肽-2

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2024-04-01 DOI: 10.1530/erc-24-0052

Laura Gerard, Céline Patte, Laurence Chardon, Valerie Hervieu, Léa Payen, Marion Allio, Claire Marx, Hugo Clermidy, Alice Durand, Patrick Mehlen, Julien Bollard, Gilles Poncet, Colette Roche, Benjamin Gibert, Thomas Walter

{"title":"Neuropilin-2 and soluble neuropilin-2 in neuroendocrine neoplasms","authors":"Laura Gerard, Céline Patte, Laurence Chardon, Valerie Hervieu, Léa Payen, Marion Allio, Claire Marx, Hugo Clermidy, Alice Durand, Patrick Mehlen, Julien Bollard, Gilles Poncet, Colette Roche, Benjamin Gibert, Thomas Walter","doi":"10.1530/erc-24-0052","DOIUrl":"https://doi.org/10.1530/erc-24-0052","url":null,"abstract":"Neuropilin-2 (NRP2), a transmembrane non-tyrosine kinase receptor, has been described as a potential critical player in the tumourigenesis of several solid cancers, and particularly in neuroendocrine neoplasms (NEN). A soluble form of NRP2 (sNRP2) has been previously described and corresponds to a truncated splice isoform. Its prognostic value has never been studied in NEN. NRP2 expression was studied by immunochemistry on tissue microarrays (n=437) and on circulating tumour cells (CTC, n=5 patients with neuroendocrine carcinoma, NEC). We described the levels of sNRP2 in 229 patients with NEN using the ELISA method to identify the factors associated with sNRP2 levels and to evaluate its prognostic role; 90 blood donors represented the healthy control group. NRP2 was found in 97% of neuroendocrine tumours (396/410) and in 74% of NEC (20/27). NRP2 was also expressed in CTC of all the studied patients. The receiver operating characteristic (ROC) analysis showed that sNRP2 had a weak capacity to discriminate between NEN patients and healthy controls [area under curve (AUC)=0.601, p=0.053]. Abnormal sNRP2 levels were associated with inflammatory syndrome, bone and peritoneal metastases, and abnormal chromogranin A levels. Patients with high sNRP2 levels (sNRP2Q3-Q4) had significantly poorer overall survival in multivariate analysis (HR 0.16, 95%CI [0.04-0.67], p=0.015). In conclusion, the present study found that sNRP2 and NRP2 could represent a new prognostic biomarker and a therapeutic target, respectively, particularly in aggressive NEN.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic disorders and insulinoma/glucagonoma 遗传性疾病和胰岛素瘤/胰高血糖素瘤

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2024-03-01 DOI: 10.1530/erc-23-0245

Francesca Marini, Francesca Giusti, Maria Luisa Brandi

引用次数: 0

Impact of Sex on Treatment Decisions and Outcome in Patients with Neuroendocrine Neoplasms 性别对神经内分泌肿瘤患者治疗决定和治疗结果的影响

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-12-01 DOI: 10.1530/erc-23-0235

Julia Beck, Alexander Siebenhüner, Damian Wild, Emanuel Christ, Julie Refardt

{"title":"Impact of Sex on Treatment Decisions and Outcome in Patients with Neuroendocrine Neoplasms","authors":"Julia Beck, Alexander Siebenhüner, Damian Wild, Emanuel Christ, Julie Refardt","doi":"10.1530/erc-23-0235","DOIUrl":"https://doi.org/10.1530/erc-23-0235","url":null,"abstract":"The influence of sex on neuroendocrine neoplasms (NENs) has been scarcely investigated. Thus, this study aimed to compare tumor characteristics, treatment decisions, and overall survival in patients with NENs, stratified by sex. The retrospective analysis of the SwissNET cohort covered NENs of gastroenteropancreatic, pulmonary, or unknown origin from 07/14 – 09/22. The analysis included 1985 patients (46% female and 54% male). Male patients presented with higher staging at time of diagnosis and with more lymph node- and bone-metastases. Surgery was performed more often in female compared to male patients (73.4% vs. 68.7%, p=0.023). Male patients received peptide receptor nuclide therapy (PRRT) earlier than female patients (7.8 months vs 13.1 months from time of diagnosis, p=0.003). The median overall survival was significantly shorter for male compared to female patients (Male: 18 years, Female: not reached, p<0.001, Hazard Ratio (HR) 1.55 [1.19-2.01], p=0.001). In conclusion, male sex was associated with worse outcome in NEN patients, likely due to more advanced tumor stage at the time of diagnosis. Further investigations are required to understand the underlying mechanisms of these sex differences.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138824197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond the 3 P’s: Adrenal involvement in MEN1 超越 3 P：MEN1 的肾上腺受累

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-12-01 DOI: 10.1530/erc-23-0162

Uriel Clemente-Gutierrez, Carolina R.c. Pieterman, Michael S. Lui, Thomas Szabo Yamashita, Andrés Tame-Elorduy, Bernice L. Huang, Aditya S. Shirali, Derek J. Erstad, Jeffrey E. Lee, Sarah B. Fisher, Paul H. Graham, Elizabeth G. Grubbs, Steven G Waguespack, Chaan S. Ng, Nancy Perrier

{"title":"Beyond the 3 P’s: Adrenal involvement in MEN1","authors":"Uriel Clemente-Gutierrez, Carolina R.c. Pieterman, Michael S. Lui, Thomas Szabo Yamashita, Andrés Tame-Elorduy, Bernice L. Huang, Aditya S. Shirali, Derek J. Erstad, Jeffrey E. Lee, Sarah B. Fisher, Paul H. Graham, Elizabeth G. Grubbs, Steven G Waguespack, Chaan S. Ng, Nancy Perrier","doi":"10.1530/erc-23-0162","DOIUrl":"https://doi.org/10.1530/erc-23-0162","url":null,"abstract":"Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients’ clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47±11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional workup (diagnoses: pheochromocytoma [n=2], adrenocorticotropic hormone–dependent hypercortisolism [n=2], hyperandrogenism [n=1], hyperaldosteronism [n=1]); surgery was indicated for 5 (83.3%; n=12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and 2 with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion’s growth rate and size. A baseline hormonal workup is recommended, and no further biochemical workup is suggested when the initial assessment shows nonfunctioning lesions.\u0000","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138740974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia-associated genetic signature in ovarian steroid cell tumor NOS. 卵巢类固醇细胞肿瘤NOS.缺氧相关基因特征。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-10-04 Print Date: 2023-11-01 DOI: 10.1530/ERC-23-0179

Angel Chao, Huei-Jean Huang, Chiao-Yun Lin, Chia-Hwa Lee, Chien-Hsing Lin, An-Shine Chao, Chyong-Huey Lai, Ting-Chang Chang, Kai-Yun Wu, Ren-Chin Wu

{"title":"Hypoxia-associated genetic signature in ovarian steroid cell tumor NOS.","authors":"Angel Chao, Huei-Jean Huang, Chiao-Yun Lin, Chia-Hwa Lee, Chien-Hsing Lin, An-Shine Chao, Chyong-Huey Lai, Ting-Chang Chang, Kai-Yun Wu, Ren-Chin Wu","doi":"10.1530/ERC-23-0179","DOIUrl":"10.1530/ERC-23-0179","url":null,"abstract":"Steroid cell tumors, not otherwise specified (SCT-NOS), are uncommon ovarian neoplasms accompanied by virilization symptoms due to hyperandrogenism, which are malignant in approximately one-third of the cases. Given the rarity of SCT-NOS, their molecular underpinnings have not yet been studied in depth. In this case series, we performed the first comprehensive analysis of the genetic landscape of this rare ovarian tumor. A detailed clinicopathological description of an index case is also provided. Over a 20-year period, a total of eight patients were seen at our institution. Total nucleic acids (RNA and DNA) were extracted from evaluable formalin-fixed, paraffin-embedded tumor specimens (n = 7) and subjected to TruSight Oncology 500 testing and/or exome sequencing. The results identified pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4. As the first comprehensive genetic analysis of SCT-NOS, this study shows that dysregulation in the hypoxia signaling pathway is a key molecular feature of this rare tumor. Clinically, long-term follow-up with periodic measurements of androgen levels should be pursued in all cases since recurrences may occur several years after the initial diagnosis.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IGF-1 axis changes with ADT and docetaxel in metastatic prostate cancer. 转移性前列腺癌症中IGF-1轴随ADT和多烯紫杉醇的变化。

IF 4.1 2区医学

Endocrine-related cancer Pub Date : 2023-10-04 Print Date: 2023-11-01 DOI: 10.1530/ERC-23-0241

Praful Ravi, Victoria Wang, Raina N Fichorova, Bradley McGregor, Xiao X Wei, Shehzad Basaria, Christopher J Sweeney

{"title":"IGF-1 axis changes with ADT and docetaxel in metastatic prostate cancer.","authors":"Praful Ravi, Victoria Wang, Raina N Fichorova, Bradley McGregor, Xiao X Wei, Shehzad Basaria, Christopher J Sweeney","doi":"10.1530/ERC-23-0241","DOIUrl":"10.1530/ERC-23-0241","url":null,"abstract":"Androgen deprivation therapy (ADT) forms the cornerstone of treatment in locally advanced and metastatic prostate cancer (PCa). Since the growth hormone-insulin-like growth factor (GH-IGF-1) axis has been implicated in prostate tumorigenesis, we aimed to evaluate the association between IGF-1 and its binding proteins on outcomes in men with metastatic PCa treated with ADT, with or without docetaxel (D). We analyzed serum samples for IGF-1 and its family proteins from baseline, 6 months post-randomization, and at the time of progression in men enrolled to receive ADT +/- D in the phase 3 CHAARTED trial. The key outcomes were time to the development of castrate-resistant prostate cancer and overall survival (OS). About 560 patients had samples available for analysis. At 6 months, significant increases in IGF-BP1 (mean Δ+27.4%, P = 0.033), IGF-BP3 (mean Δ+10.3%, P < 0.001), and IGF-BP4 (mean Δ+31.1%, P < 0.001) were seen in the ADT + D group, while the ADT group showed an increase in IGF-BP3 (mean Δ+5.5%, P = 0.015). A higher IGF-1:IGF-BP1 ratio at baseline and after 6 months was associated with improved OS in both the ADT (baseline: hazard ratio (HR) = 0.77, P = 0.026; 6 months: HR = 0.83, P = 0.036) and ADT + D groups (baseline: HR = 0.78, P = 0.04; 6 months: HR = 0.81, P = 0.018). Patients with a log10IGF-1:IGF-BP1 ratio >1.3 at baseline had improved OS when meta-analyzed with data from a prior cohort (HR = 0.71). A higher baseline and 6-month IGF-1:IGF-BP1 ratio was associated with better OS. Further exploration of the IGF-1 axis will be important to assess its role as a predictive biomarker and to target this axis in therapeutic trials.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10163321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MicroRNA regulation of the serine synthesis pathway in endocrine-resistant breast cancer cells. 内分泌耐药乳腺癌症细胞丝氨酸合成途径的微小RNA调节。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-27 Print Date: 2023-11-01 DOI: 10.1530/ERC-23-0148

Belinda J Petri, Kellianne M Piell, Ali E Wilt, Alexa D Howser, Laura Winkler, Mattie R Whitworth, Bailey L Valdes, Norman L Lehman, Brian F Clem, Carolyn M Klinge

{"title":"MicroRNA regulation of the serine synthesis pathway in endocrine-resistant breast cancer cells.","authors":"Belinda J Petri, Kellianne M Piell, Ali E Wilt, Alexa D Howser, Laura Winkler, Mattie R Whitworth, Bailey L Valdes, Norman L Lehman, Brian F Clem, Carolyn M Klinge","doi":"10.1530/ERC-23-0148","DOIUrl":"10.1530/ERC-23-0148","url":null,"abstract":"Despite the successful combination of therapies improving survival of estrogen receptor α (ER+) breast cancer patients with metastatic disease, mechanisms for acquired endocrine resistance remain to be fully elucidated. The RNA binding protein HNRNPA2B1 (A2B1), a reader of N(6)-methyladenosine (m6A) in transcribed RNA, is upregulated in endocrine-resistant, ER+ LCC9 and LY2 cells compared to parental MCF-7 endocrine-sensitive luminal A breast cancer cells. The miRNA-seq transcriptome of MCF-7 cells overexpressing A2B1 identified the serine metabolic processes pathway. Increased expression of two key enzymes in the serine synthesis pathway (SSP), phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate dehydrogenase (PHGDH), correlates with poor outcomes in ER+ breast patients who received tamoxifen (TAM). We reported that PSAT1 and PHGDH were higher in LCC9 and LY2 cells compared to MCF-7 cells and their knockdown enhanced TAM sensitivity in these-resistant cells. Here we demonstrate that stable, modest overexpression of A2B1 in MCF-7 cells increased PSAT1 and PHGDH and endocrine resistance. We identified four miRNAs downregulated in MCF-7-A2B1 cells that directly target the PSAT1 3'UTR (miR-145-5p and miR-424-5p), and the PHGDH 3'UTR (miR-34b-5p and miR-876-5p) in dual luciferase assays. Lower expression of miR-145-5p and miR-424-5p in LCC9 and ZR-75-1-4-OHT cells correlated with increased PSAT1 and lower expression of miR-34b-5p and miR-876-5p in LCC9 and ZR-75-1-4-OHT cells correlated with increased PHGDH. Transient transfection of these miRNAs restored endocrine-therapy sensitivity in LCC9 and ZR-75-1-4-OHT cells. Overall, our data suggest a role for decreased A2B1-regulated miRNAs in endocrine resistance and upregulation of the SSP to promote tumor progression in ER+ breast cancer.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10495673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0