Molecular tumorigenesis of the skin

Abstract

Skin tumors are supposed to develop through accumulations of genetic and/or epigenetic events in normal cells of the skin. Among them, we focus on common skin tumors, including benign, seborrheic keratosis, and malignant, squamous cell carcinoma and melanoma. Many important molecules have been detected on the molecular tumorigenesis of each of them to date, and some drugs targeted for their molecules have been already developed. We review updates on the molecular tumorigenesis of these tumors with our current works.

Histopathological study of perilesional skin in patients diagnosed with nonmelanoma skin cancer

“…The aforementioned data are further supported by molecular studies demonstrating strong evidence for the association of sunlight and SCC (thymidine dimers and C>T transitions in p53 and other important molecules), whereas it is still unclear whether there is such an association for BCC (lack of UVB signatures at the PTCH/SMO sites) …”

Assessment of BCL-2 expression in actinic keratosis, keratoacanthoma and seborrheic keratosis cases

“…The outer layer of the skin comprises the epidermis. The epidermis contains epidermal keratinocytes and low numbers of melanocytes distributed towards the basal layer (1).…”

“…Bcl-2 is expressed in tissue during physiologic and pathologic events in the intrauterine and extrauterine period, and is an apoptosis inhibitor ensuring cell viability without causing cell proliferation (5,6). It prevents or clearly reduces cell death begun by activation of intrinsic and extrinsic pathways by various stimuli like radiation, ultraviolet (UV), p53, chemotherapeutic medication and reactive oxygen radicals (1,6).…”

Skin Specific Cells and UVB Damage An experimental assessment

“…NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), impart fundamental features based on the fact that both disorders result from normal keratinocytes founded in epidermis, by a multistage process which implies activation/inactivation of some genes (e.g. oncogenes, tumor suppressor genes) being related mainly with UV radiation and immunosuppression [7][8][9][10]. The major difference between the two classes of NMSC consist in the ability to metastasize: BCC seldom metastasize and derive from normal/healthy skin while SCC often metastasize and derive from attendant lesions, like actinic keratosis which occur after repeated sun exposure [8].…”

“…MSC, is the most aggressive type of skin cancer, arises from melanocytes, cells liable for skin pigmentation and photoprotection, during malignant alteration. Molecular tumorigenesis plays a crucial role, thereby depending on it is classified as follows: skin melanoma not associated with chronic sun-induced damage, skin melanoma with sun-induced damage, acral melanoma and mucosal melanoma [7].…”