The overexpression and altered localization of the atypical protein kinase C lambda/iota in breast cancer correlates with the pathologic type of these tumors.
Breast cancer is one of the common malignant diseases among women in Japan as well as in western countries, and its incidence continues to increase. Normal mammary duct epithelial cells exhibit a well-organized apicobasal polarity, which forms the basis for their specific structure and function. Although the loss of epithelial cell polarity is one of the major changes that occur during the progression of tumor cells, including breast cancer, the underlying molecular mechanisms for this, as well as their relationship to other changes such as increased proliferation and metastasis, remain to be elucidated. The atypical protein kinase C lambda/iota (aPKC lambda/iota) is involved in several signal transduction pathways, including the establishment of epithelial cell polarity. In this study we evaluated the expression and localization of aPKC lambda/iota in breast cancer by immunohistochemistry and compared our findings with the clinicopathologic factors associated with the tumor specimens. We detected aPK Clambda/iota protein overexpression in 88 of the 110 breast cancer cases (80.0%) under study, expect for decreased expression in a few cases. The immunoreactivity of aPK Clambda/iota was generally weak in ductal carcinoma in situ, but strong in invasive ductal carcinoma (IDC; P = .022). The correlation between apical or cytoplasmic aPKC lambda/iota localization and tumor pathologic type (ie, atypical ductal hyperplasia, ductal carcinoma in situ. or IDC) was also demonstrated (P < .001). These results thus indicate that the normal apicobasal polarity is lost upon the progression of a breast lesion to IDC. This is also the first evidence to show aPKC lambda/iota overexpression in breast cancer and demonstrates that its localization is associated with the trend of pathologic type of the tumor.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Yasuyuki
Y
Kojima
Kazunori
K
Akimoto
Yoji
Y
Nagashima
Hitoshi
H
Ishiguro
Sumiko
S
Shirai
Takashi
T
Chishima
Yasushi
Y
Ichikawa
Takashi
T
Ishikawa
Takeshi
T
Sasaki
Yoshinobu
Y
Kubota
Yoshiaki
Y
Inayama
Ichiro
I
Aoki
Shigeo
S
Ohno
Hiroshi
H
Shimada
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000556:secondary / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology / Q000556:secondary / Q000628:therapy; D016764:Cell Polarity; D003131:Combined Modality Therapy; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D000099293:Protein Kinase C-lambda
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda