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Am J Transl Res 2013;5(1):80-91
Original Article
Cav1 inhibits benign skin tumor development in a two-stage
carcino-genesis model by suppressing epidermal proliferation
Casey Trimmer, Federica Sotgia, Michael P Lisanti, Franco Capozza
Department of Cancer Biology/Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University,
Philadelphia, PA, USA; Breakthrough Breast Cancer Research Unit, Institute of Cancer Sciences, University of
Manchester, UK
Received November 28, 2012; Accepted December 30, 2012; Epub January 21, 2013; Published January 30, 2013
Abstract: Caveolin-1 (Cav1) is the main protein component of the membrane lipid rafts caveolae. Cav1 serves as
a scaffolding protein that compartmentalizes a multitude of signaling molecules and sequesters them in their
inactive state. Due to its function in the negative regulation of signal transduction, loss of Cav1 has been
implicated in the pathogenesis of many cancers, but its role in cutaneous squamous cell carcinoma (cSCC) is
largely unexplored. cSCC is a multi-stage disease characterized by the development of benign, premalignant
lesions and their progression into malignant cancer. Here, we use a two-stage carcinogenesis protocol to
elucidate the function of Cav1 in the different stages of benign papilloma development: initiation and promotion.
First, we demonstrate that Cav1 knock-out (KO) mice are more susceptible to benign papilloma development
after being subjected to a DMBA/TPA initiation/promotion protocol. Treatment of wild-type (WT) and Cav1 KO mice
with DMBA alone shows that both groups have similar rates of apoptosis. In contrast, treatment of these groups
with TPA alone indicates that Cav1 KO mice are more susceptible to promoter treatment as evidenced by
increased epidermal proliferation. Furthermore, primary keratinocytes isolated from Cav1 KO mice have a
proliferative advantage over WT keratinocytes in both low- and high-calcium medium, conditions that promote
proliferation and induce differentiation, respectively. Collectively, these data indicate that Cav1 functions to
suppress proliferation in the epidermis, and loss of this function promotes the development of benign skin
tumors. (AJTR1211010).
Keywords: Cav1, caveolin, skin cancer, skin, two stage carcinogenesis
Address correspondence to: Dr. Franco Capozza, Dept. of Cancer Biology/Stem Cell Biology and Regenerative
Medicine , Kimmel Cancer Cen-ter, Thomas Jefferson University, 940 BLSB, 233 S 10th Street, Philadelphia, PA
19107, USA. Phone: 215-503-9288; Fax: 215-923-1098; E-mail: Franco.Capozza@jefferson.edu
Original Article
Cav1 inhibits benign skin tumor development in a two-stage
carcino-genesis model by suppressing epidermal proliferation
Casey Trimmer, Federica Sotgia, Michael P Lisanti, Franco Capozza
Department of Cancer Biology/Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University,
Philadelphia, PA, USA; Breakthrough Breast Cancer Research Unit, Institute of Cancer Sciences, University of
Manchester, UK
Received November 28, 2012; Accepted December 30, 2012; Epub January 21, 2013; Published January 30, 2013
Abstract: Caveolin-1 (Cav1) is the main protein component of the membrane lipid rafts caveolae. Cav1 serves as
a scaffolding protein that compartmentalizes a multitude of signaling molecules and sequesters them in their
inactive state. Due to its function in the negative regulation of signal transduction, loss of Cav1 has been
implicated in the pathogenesis of many cancers, but its role in cutaneous squamous cell carcinoma (cSCC) is
largely unexplored. cSCC is a multi-stage disease characterized by the development of benign, premalignant
lesions and their progression into malignant cancer. Here, we use a two-stage carcinogenesis protocol to
elucidate the function of Cav1 in the different stages of benign papilloma development: initiation and promotion.
First, we demonstrate that Cav1 knock-out (KO) mice are more susceptible to benign papilloma development
after being subjected to a DMBA/TPA initiation/promotion protocol. Treatment of wild-type (WT) and Cav1 KO mice
with DMBA alone shows that both groups have similar rates of apoptosis. In contrast, treatment of these groups
with TPA alone indicates that Cav1 KO mice are more susceptible to promoter treatment as evidenced by
increased epidermal proliferation. Furthermore, primary keratinocytes isolated from Cav1 KO mice have a
proliferative advantage over WT keratinocytes in both low- and high-calcium medium, conditions that promote
proliferation and induce differentiation, respectively. Collectively, these data indicate that Cav1 functions to
suppress proliferation in the epidermis, and loss of this function promotes the development of benign skin
tumors. (AJTR1211010).
Keywords: Cav1, caveolin, skin cancer, skin, two stage carcinogenesis
Address correspondence to: Dr. Franco Capozza, Dept. of Cancer Biology/Stem Cell Biology and Regenerative
Medicine , Kimmel Cancer Cen-ter, Thomas Jefferson University, 940 BLSB, 233 S 10th Street, Philadelphia, PA
19107, USA. Phone: 215-503-9288; Fax: 215-923-1098; E-mail: Franco.Capozza@jefferson.edu
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