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The Role of Cathepsins in Involution and Breast Cancer

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Abstract

Cysteine cathepsins are proteolytic enzymes that reside in endolysosomal vesicles. Some are expressed constitutively while others are transcriptionally regulated. However, the expression and subcellular localization of cathepsins changes during cancer progression and cathepsins have been shown to be causally involved in various aspects of tumorigenesis including metastasis. The use of mouse models of breast cancer genetically ablated for cathepsin B has shown that both the growth of the primary tumor and the extend of lung metastasis is reduced by the loss of cathepsin B. The role of cathepsins in involution of the mammary gland has received little attention although it is clear that cathepsins are involved in tissue remodeling in the second phase of involution. We discuss here the roles of cathepsins and their endogenous inhibitors in breast tumorigenesis and post-lactational involution.

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Abbreviations

Stat:

Signal transducer and activator of transcription

h:

hours

Fig.:

figure

ROS:

reactive oxygen species

ACD:

autophagic cell death

TNFα:

tumor necrosis factor alpha

LMP:

lysosomal membrane permeabilization

RANKL:

receptor activator of nuclear factor-kappaB ligand

iNOS:

inducible nitric oxide synthase

kDa:

kiloDaltons

MMTV-PyMT:

mouse mammary tumor virus-Polyoma middle T antigen

Cat:

cathepsin

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Acknowledgements

Work in the authors’ laboratory is supported by the BBSRC, the Breast Cancer Campaign and the AICR. PK is supported by a Pathology Department PhD studentship. We thank Drs Blandine Kedjouar and Jeremy Skepper for the images shown in Fig. 1b and c respectively. We are grateful to Professor Philip Ashton-Rickardt for his helpful comments on this manuscript.

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  1. Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, MA, CB2 1QP, USA

    Christine J. Watson & Peter A. Kreuzaler

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  1. Christine J. Watson
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  2. Peter A. Kreuzaler
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Correspondence to Christine J. Watson.

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Watson, C.J., Kreuzaler, P.A. The Role of Cathepsins in Involution and Breast Cancer. J Mammary Gland Biol Neoplasia 14, 171–179 (2009). https://doi.org/10.1007/s10911-009-9126-8

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