Regulation of PTHrP and PTH/PTHrP receptor by extracellular Ca2+ concentration and hormones in the breast cancer cell line 8701-BC.
It was previously reported that 8701-BC breast tumour cells express the gene for parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor (PTHrP-R) and release immunoreactive PTHrP (iPTHrP) into the extracellular medium. Since the regulation of PTHrP and PTHrP-R by breast cancer cells has been poorly investigated so far, we have chosen the 8701-BC cell line as a model system to investigate whether alterations in the extracellular Ca2+ concentration ([Ca2+]e) and treatment with some well-known differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, progesterone, prolactin, all-trans retinoic acid and transforming growth factor-beta1 might (i) modulate quantitatively the release of iPTHrP, (ii) affect the PTHrP promoter usage and mRNA splicing patterns, and (iii) modify the expression of PTHrP-R. The data obtained indicate that 8701-BC cells are potentially able to utilise different start sites and mRNA splicing patterns for PTHrP transcription, and respond to variations of [Ca2+]e and to the addition of two hormones, hydrocortisone and progesterone, with modifications in the extracellular amount of iPTHrP. Moreover, expression of PTHrP-R is also modulated by changes of [Ca2+]e or treatment with hydrocortisone. This indicates that the 8701 -BC cell line is a suitable in vitro model for further studies on the complex molecular regulation of the PTHrP/PTHrP-R pair in breast cancer.
Luparello
C
C
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Viale delle Scienze, Italy.
Santamaria
F
F
Schilling
T
T
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000494:pharmacology*; D018387:Codon, Initiator; D005110:Extracellular Space / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020033:Protein Isoforms / Q000096:biosynthesis / Q000187:drug effects; D011506:Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D018016:Receptors, Parathyroid Hormone / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018387:Codon, Initiator; D006728:Hormones; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D018016:Receptors, Parathyroid Hormone; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D002118:Calcium