title: Divergent expression of L-type amino acid transporter 1 during uterine cervical carcinogenesis.
abstract: L-type amino acid transporter 1 (LAT1) is a Na⁺-independent neutral amino acid transporter that has an essential role in cell proliferation. Although LAT1 expression is observed in various tumor cell lines and immunohistochemical expression of LAT1 has been investigated in carcinomas of various organs, LAT1 expression in uterine cervical neoplasm has not been reported. Therefore, in the present study, we immunohistochemically analyzed LAT1 expression along with the well-known markers of cervical carcinogenesis Ki-67 and p16 in normal uterine cervical mucosa (49 specimens) as well as cervical intraepithelial neoplasia (17 mild or moderate dysplasias and 19 severe dysplasias or carcinomas in situ) and invasive carcinomas (17 squamous cell carcinomas and 9 adenocarcinomas). LAT1 expression was limited to the basal layer of normal squamous epithelium, and it was significantly decreased in cervical intraepithelial neoplasia (P < .001), generally paralleled by increased expression of Ki-67 and p16. Interestingly, in invasive squamous cell carcinoma, LAT1 expression again increased especially at the invasive fronts (P < .001), whereas Ki-67 and p16 expressions were almost unchanged relative to noninvasive neoplasia. Although virtually no LAT1 expression was demonstrated in normal uterine cervical glands, LAT1 expression was observed in some adenocarcinomas (P < .001). The present study suggests that LAT1 expression decreases because of human papillomavirus infection as reflected by p16 overexpression in cervical intraepithelial neoplasia, whereas LAT1 expression in invasive carcinoma is associated with acquired malignant potential.
authors.affiliation: Kyorin University School of Medicine, Tokyo 181-8611, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Uno
authors.forename: Haruki
authors.initials: H
authors.lastname: Kuwabara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Terado
authors.forename: Kaoruko
authors.initials: K
authors.lastname: Kojima
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawakami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamma
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurata
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D027283:Large Neutral Amino Acid-Transporter 1