Pregnancy and weaning regulate human maternal liver size and function

During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a prometastatic niche. These data suggest a mechanism for increased liver metastasis in breast cancer patients with recent childbirth. It is unknown whether the human liver changes in size and function during pregnancy and weaning. In this study, abdominal imaging was obtained in healthy women at early and late pregnancy and postwean. During pregnancy time points, glucose production and utilization and circulating bile acids were measured. Independently of weight gain, most women’s livers increased in size with pregnancy, then returned to baseline postwean. Putative roles for bile acids in liver growth and regression were observed. Together, the data support the hypothesis that the human liver is regulated by reproductive state with growth during pregnancy and volume loss postwean. These findings have implications for sex-specific liver diseases and for breast cancer outcomes.

Download Full-text

Pregnancy and weaning regulate human maternal liver size and function

10.1101/2021.02.18.431862 ◽

2021 ◽

Author(s):

Alexandra Q Bartlett ◽

Kimberly K Vesco ◽

Jonathan Q Purnell ◽

Melanie Francisco ◽

Erica Goddard ◽

...

Keyword(s):

Bile Acids ◽

Human Liver ◽

Glucose Production ◽

Late Pregnancy ◽

Endogenous Glucose Production ◽

Hepatocyte Proliferation ◽

Breast Cancer Patients ◽

Liver Size ◽

Liver Growth ◽

And Function

AbstractBACKGROUNDDuring pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a pro-metastatic niche. These data suggest a mechanism for increased liver metastasis in postpartum breast cancer patients.OBJECTIVESInvestigate if the human liver changes in size and function during pregnancy and weaning.METHODSAbdominal imaging was obtained in healthy women at early and late pregnancy, and post-wean. During pregnancy time points, endogenous glucose production was measured and fasting blood taken to measure bile acids.RESULTSIndependent of weight gain, most women’s livers increased in size with pregnancy, returning to baseline post-wean. Putative roles for bile acids in liver growth were observed in pregnant women and rodents.CONCLUSIONSThe human liver is regulated by reproductive state with growth during pregnancy and volume loss post-wean. These findings may have broad implications for sex-specific liver diseases and cancer.

Download Full-text

Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses

Cells ◽

10.3390/cells9102167 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2167

Author(s):

Brock Humphries ◽

Zhishan Wang ◽

Chengfeng Yang

Keyword(s):

Breast Cancer ◽

Membrane Trafficking ◽

Rho Gtpases ◽

Migration And Invasion ◽

Breast Cancer Patients ◽

Cancer Initiation ◽

Cell Type Specific ◽

And Function ◽

Therapeutic Responses

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, tumor suppressor functions of Rho GTPases have also been revealed, suggesting a context and cell-type specific function for Rho GTPases in cancer. This review aims to summarize recent progresses in our understanding of the regulation and functions of Rho GTPases, specifically in the context of breast cancer. The potential of Rho GTPases as therapeutic targets and prognostic tools for breast cancer patients are also discussed.

Download Full-text

Phenotype And Function Of Dendritic Cells Derived From Breast Cancer Patients

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2009.12.084 ◽

2010 ◽

Vol 125 (2) ◽

pp. AB14

Author(s):

A.Y. Hancharou ◽

L.P. Titov ◽

L.A. Putyrski ◽

Y.L. Putyrski ◽

L.M. DuBuske

Keyword(s):

Breast Cancer ◽

Dendritic Cells ◽

Cancer Patients ◽

Breast Cancer Patients ◽

And Function

Download Full-text

Prolactin receptor in breast cancer: marker for metastatic risk

Journal of Molecular Endocrinology ◽

10.1530/jme-16-0150 ◽

2016 ◽

Vol 57 (4) ◽

pp. R153-R165 ◽

Cited By ~ 11

Author(s):

Carrie S Shemanko

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Prolactin Receptor ◽

Osteoclast Formation ◽

Receptor Signaling ◽

Breast Cancer Patients ◽

Receptor Isoforms ◽

Receptor Biology ◽

Metastatic Risk ◽

And Function

Prolactin and prolactin receptor signaling and function are complex in nature and intricate in function. Basic, pre-clinical and translational research has opened up our eyes to the understanding that prolactin and prolactin receptor signaling function differently within different cellular contexts and microenvironmental conditions. Its multiple roles in normal physiology are subverted in cancer initiation and progression, and gradually we are teasing out the intricacies of function and therapeutic value. Recently, we observed that prolactin has a role in accelerating the time to bone metastasis in breast cancer patients and identified the mechanism by which prolactin stimulated breast cancer cell-mediated lytic osteoclast formation. The possibility that the prolactin receptor is a marker for metastasis, and specifically bone metastasis, is one that may have to be put into the context of the different variants of prolactin, different prolactin receptor isoforms and intricate signaling pathways that are regulated by the microenvironment. The more complete the picture, the better one can test biomarker identity and design clinical trials to test therapeutic intervention. This review will cover the recent advances and highlight the complexity of prolactin receptor biology.

Download Full-text

Identification of γ-aminobutyric acid receptor subunit types in human and rat liver

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.279.4.g733 ◽

2000 ◽

Vol 279 (4) ◽

pp. G733-G739 ◽

Cited By ~ 22

Author(s):

Ronit Erlitzki ◽

Yuewen Gong ◽

Manna Zhang ◽

Gerald Minuk

Keyword(s):

Partial Hepatectomy ◽

Rat Liver ◽

Human Liver ◽

Pcr Amplification ◽

Hepatocyte Proliferation ◽

Mammalian Brain ◽

Quiescent State ◽

Receptor Subunit ◽

Isolated Rat Hepatocytes ◽

Liver Growth

GABA is a potent inhibitory neurotransmitter that binds to heterooligomeric receptors in the mammalian brain. In a previous study, we documented specific GABA binding to isolated rat hepatocytes that resulted in inhibition of hepatocyte proliferation. The purpose of the present study was to define the nature of hepatic GABAA receptors and to document their expression during rapid liver growth (after partial hepatectomy). PCRs with gene-specific primers derived from published sequences were performed with Marathon-ready human and rat liver cDNA. Two GABAA receptor subunit types (β3 and ε) were expressed in human liver and one subunit type (β3) in rat liver. PCR amplification of the human GABAA receptorβ3-subunit produced a single product (molecular mass 53–59 kDa). In the case of the ε-subunit, two PCR products were identified. After partial hepatectomy, GABAA receptorβ3-subunit expression inversely correlated with regenerative activity ( r = −0.527, P = 0.006). In conclusion, these results indicate that in the human liver GABAA receptors consist of the β3- and ε-subunit types, whereas in the rat liver only the β3-subunit type is expressed. The results also support the hypothesis that GABAergic activity serves to maintain hepatocytes in a quiescent state.

Download Full-text

High-risk breast cancer patients: comparison of lymphocyte phenotypes and function in vitro

Breast Cancer Research ◽

10.1186/bcr369 ◽

2001 ◽

Vol 3 (S1) ◽

Author(s):

S Mohrmann ◽

A Oletzki ◽

A Karaoglu ◽

U Nitz ◽

U Koldovsky

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Breast Cancer Patients ◽

And Function ◽

Lymphocyte Phenotypes ◽

High Risk Breast Cancer ◽

High Risk Breast ◽

Risk Breast Cancer

Download Full-text

The noncoding RNAs SNORD50A and SNORD50B-mediated TRIM21-GMPS interaction promotes the growth of p53 wild-type breast cancers by degrading p53

Cell Death and Differentiation ◽

10.1038/s41418-021-00762-7 ◽

2021 ◽

Author(s):

Xi Su ◽

Chao Feng ◽

Simeng Wang ◽

Liang Shi ◽

Qingqing Gu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Wild Type ◽

Functional Studies ◽

Cycle Arrest ◽

Putative Tumor Suppressor ◽

And Function

AbstractSmall nucleolar RNA SNORD50A and SNORD50B (SNORD50A/B) has been reported to be recurrently deleted and function as a putative tumor suppressor in different types of cancer by binding to and suppressing the activity of the KRAS oncoproteins. Its deletion correlates with poorer patient survival. However, in this study, we surprisingly found that SNORD50A/B loss predicted a better survival in breast cancer patients carrying wild-type p53. Functional studies showed that SNORD50A/B deletion strongly inhibited the proliferation, migration, invasion and tumorigenic potential, and induced cell cycle arrest and apoptosis in p53 wild-type breast cancer cells, while exerted the opposite effects in p53 mutated breast cancer cells. This was also supported by ectopically expressing SNORD50A/B in both p53 wild-type and mutated breast cancer cells. Mechanistically, SNORD50A/B clearly enhances the interaction between E3 ubiquitin ligase TRIM21 and its substrate GMPS by forming a complex among them, thereby promoting GMPS ubiquitination and its subsequent cytoplasmic sequestration. SNORD50A/B deletion in p53 wild-type breast cancer cells will release GMPS and induce the translocation of GMPS into the nucleus, where GMPS can recruit USP7 and form a complex with p53, thereby decreasing p53 ubiquitination, stabilizing p53 proteins, and inhibiting malignant phenotypes of cancer cells. Altogether, the present study first reports that SNORD50A/B plays an oncogenic role in p53 wild-type breast cancers by mediating TRIM21-GMPS interaction.

Download Full-text