Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is the most commonly diagnosed cancer among United States (US) women. Established risk factors explain only about 13% of breast cancer incidence among women in the US. Thus, the cause of most cases of breast cancer remains unknown. In postmenopausal women, serum calcium (Ca) and serum magnesium (Mg) play an important role in skeletal health, cell proliferation and cancer. Mg is essential for DNA duplication and repair and Mg deficiency favors DNA mutations leading to carcinogenesis. Dietary intake of Mg in the US is less than the recommended amount, and the deficit is more pronounced in older individuals where gastrointestinal and renal mechanisms for Mg conservation are not as efficient. Furthermore, healthy postmenopausal women are frequently recommended to take supplemental Ca, but not Mg and vitamin D to maintain bone and overall health. Most women with hormone sensitive breast cancer are recommended to take aromatase inhibitors, which causes bone loss and thus are generally prescribed Ca and vitamin D, but not Mg. Although the association between serum Ca and breast cancer risk remains controversial, we hypothesize that this may be because Mg levels have not been accounted for. Mg level directly influences transient receptor potential melastatin 7 (TRPM7) related Ca influx, calcium-adenosine triphosphatase (Ca-ATP) levels, and cell proliferation, and thereby could lead to cancer. Thus a high serum Ca/Mg ratio is more appropriate and alterations in this ratio could lead to increased development of new and recurrent breast cancer.
 ...
PMID:Does a higher ratio of serum calcium to magnesium increase the risk for postmenopausal breast cancer? 2037 Nov 55

Suboptimal cellular conditions result in the accumulation of unfolded proteins in the endoplasmic reticulum (ER) and trigger ER stress. In this study, we investigated the effects of follicle stimulating hormone (FSH) on ER stress in granulosa cells (GCs) obtained from 3-week-old female C57BL6 mice 24 or 48 hours after intraperitoneal injection of 5 IU pregnant mare's serum gonadotropin (PMSG), and in primary mouse GCs in culture treated with FSH (10-100 mIU/mL) for 24 or 48 hours. Moreover, mouse GCs in culture were treated with tunicamycin (Tm) or thapsigargin (Tp), which induce ER stress by inhibiting N-glycosylation of ER proteins and ER calcium adenosine triphosphatase, respectively, and their response to FSH was evaluated. We found that FSH attenuated ER stress in mouse GCs in vivo and in vitro; messenger RNA levels of ER stress-associated genes Xbp1s, Atf6, Chop, and Casp12 were decreased upon exposure to FSH/PMSG. Activating transcription factor 4 protein levels also demonstrated consistent decrease following FSH stimulation. Both Tm and Tp treatments inhibited FSH response, ER stress-induced cells did not show any change in estradiol levels in response to FSH, whereas in untreated GCs, estradiol production increased 3-fold after incubation with FSH for 60 hours. Furthermore, ER stress-induced cells failed to demonstrate aromatase (Cyp19a1) expression upon exposure to FSH. Importantly, under high-ER stress conditions FSH stimulation was unable to downregulate the expression of ER stress-associated genes. Our findings suggest that FSH decreases ER stress in GCs under physiologic conditions. However, under conditions that cause a significant increase in ER stress, FSH response is attenuated.
...
PMID:Cross-Talk Between FSH and Endoplasmic Reticulum Stress: A Mutually Suppressive Relationship. 2634 52