**Acknowledgement**

Some of the referred experimental work was supported by OTKA-81522 (for GMN) and by the TÁMOP-4.2.2.A-11/1/KONV-2012-0025 project (for MV).

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**Chapter 11** 

© 2013 Ginsburg et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Prolactin Receptor Isoforms** 

**in Human Breast Cancer** 

Erika Ginsburg, Christopher D. Heger, Paul Goldsmith and Barbara K. Vonderhaar

http://dx.doi.org/10.5772/54217

growth remains to be determined.

**2. Problem statement** 

**1. Introduction** 

Additional information is available at the end of the chapter

Prolactin (PRL) is a polypeptide hormone secreted by the anterior pituitary responsible for the growth and differentiation of the normal mammary gland and plays a role in breast cancer. It functions systemically as an endocrine factor, but PRL may also act in an autocrine/paracrine fashion in a number of other tissues. Studies in both pre- and post-menopausal women have determined a significant increased risk for breast cancer for those with serum PRL in the highest quartile [6, 7]. PRL, acting through its receptors, has been shown to increase cell proliferation and decrease apoptosis in breast cancer cells *in vitro* [3, 8]. PRL also acts as a proangiogenic factor in mammary tissues [9]. PRL exerts its effects by binding to its receptors on the surface of normal human breast epithelial and cancer cells, initiating the Jak2/Stat5, PI3K,

The PRL receptor (PRLR) is a member of the class I cytokine/hematopoietic receptor superfamily. A single hydrophobic transmembrane region separates the extracellular ligand-binding domain from the intracellular signaling domain. Five cell-associated PRLR isoforms differ only in their C-terminal cytoplasmic domains [1, 3]. The three major isoforms (long, LF; short 1a and 1b, SF1a and SF1b, respectively) are regulated by PRL itself. LF signals for many functions including growth and differentiation, whereas SF1a and SF1b act as dominant-negatives for differentiation [1, 2]. The role of the short forms in breast cell

Studies from our laboratory [1] and from others [2] have demonstrated that three specific isoforms of the PRLR are expressed in both normal and cancerous breast cells and tissues. We recently developed and characterized PRLR isoform specific polyclonal antibodies that

and reproduction in any medium, provided the original work is properly cited.

and mitogen-activated protein kinase (MAPK) signaling pathways [3].


**Chapter 11** 
