Disease relevance of Stat5a

• High Stat5a nuclear expression was closely correlated with the higher-grade carcinomas [1].
• Stat5a nuclear expression was also detected in intraductal proliferations (10 of 21 lesions) and in ductal carcinomas in situ (13 of 15 lesions) [1].
• Stat5a nuclear expression was detected in ductal and lobular carcinomas and DCIS at a frequency of 48% (15/31), 33% (2/6), and 40% (2/5), respectively [1].

High impact information on Stat5a

• Interleukin 2 activates STAT5 transcription factor (mammary gland factor) and specific gene expression in T lymphocytes [2].
• A growth hormone-inducible nuclear factor complex (GHINF), affinity-purified using the growth hormone response element (GHRE) from the promoter of rat serine protease inhibitor 2.1, was found to contain Stat5a and -5b, as well as additional components [3].
• On the other hand, two recently identified and highly homologous Stat5a and Stat5b proteins lack this putative mitogen-activated protein kinase phosphorylation site [4].
• No Stat5a/b phosphothreonine was detected [4].
• The C/EBP sites are located in close proximity to the previously characterized binding sites for the prolactin-inducible mammary gland factor/signal transducer and activator of transcription-5, the nuclear factor YY1, and the glucocorticoid receptor [5].

Chemical compound and disease context of Stat5a

• In the current study, Stat5a expression was examined immunohistochemically in carcinomas induced by the chemical carcinogens 7,12-dimethylbenz[a]anthracene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [1].

Biological context of Stat5a

• The levels of Stat5a increased during pregnancy, were highest in late pregnancy, and then, unexpectedly, decreased during lactation, the time at which the highest levels of milk protein gene expression are observed [6].
• Latent cytoplasmic Stat5a is activated by tyrosine phosphorylation and following dimerization undergoes nuclear import [1].
• Partial cDNAs encoding the SH2 domain of rat Stat5a and Stat5b and the zinc finger domain of rat Yy1 have been cloned by an RT-PCR based approach [7].

Anatomical context of Stat5a

• Surprisingly, Stat5a mRNA and protein were readily detected both in virgin rats and after mammary gland involution [6].
• A polyclonal antibody to a carboxy-terminal peptide of Stat5a1 was generated and used to measure the level of this isoform during mammary gland development and after PRL induction in COS cells transiently transfected with Stat5a and the long form of the PRL receptor [6].

Other interactions of Stat5a

• Through mutational analysis, a single nucleotide difference between the ERalpha and ERbeta Stat5 response elements was shown to be responsible for the lack of Stat5a-mediated stimulation of ERbeta [8].

Analytical, diagnostic and therapeutic context of Stat5a

• Western and gel shift analysis revealed that E(2)-bound ERalpha decreased the tyrosine phosphorylation and DNA-binding activity of Stat5a, indicating that the inhibitory effect of E(2) was mediated, at least in part, by interfering with PRL-mediated signal transduction [9].
• We now show that signal transducer and activator of transcription-5a (Stat5a) and Stat5b become tyrosine phosphorylated in response to PRL stimulation in rat prostate using prostate organ culture as an experimental model [10].

References