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Human prolactin receptor isoforms in breast cancer

Human prolactin receptor isoforms in breast cancer

FASEB Journal 17(4-5): Abstract No. 322-2

Prolactin plays an essential role in the development of rodent mammary tumors, and is a potent mitogen in normal and cancerous breast tissues/cells. It has also been postulated to be involved in breast cancer development. To investigate putative mechanism(s) participating in breast tumorogenesis, we analyzed the expression of prolactin receptors, including the long receptor form (LF, stimulatory) and two novel short forms (SF) derived from alternative splicing that are inhibitory of the LF. Southern analysis of breast cancer profiling arrays revealed that 29 patients (I) expressed an elevated LF, 10 patients (II) showed decreased LF, and 8 patients (III) had no change relative to adjacent normal tissue. Their respective SF expression was increased in 21 patients of group I and generally decreased in groups II and III. However, the ratio of SF to LF was significantly decreased in 76 % of the breast tumors, and distributed evenly among the groups. Differential expression of PRLR isoforms was confirmed by real time PCR using human breast matched cDNA pairs; where 4 of 5 individuals showed a significant decrease in the ratio of SF to LF in the tumor tissue. Since SFs act as dominant negative regulators of the stimulatory actions of the LF in vitro, their relatively reduced expression in cancer could cause gradations of unopposed prolactin-mediated LF stimulatory function and contribute to breast tumor development/progression.))).

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