This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shoji, M. Articles by Kameya, T. Search for Related Content PubMed PubMed Citation Articles by Shoji, M. Articles by Kameya, T.

(American Journal of Pathology. 1999;154:909-918.)
© 1999 American Society for Investigative Pathology

Regular Articles

Tumor Extension and Cell Proliferation in Adenocarcinomas of the Lung

Mitsuhiko Shoji* , Yoh Dobashi* , Shojiroh Morinaga , Shi-Xu Jiang* and Toru Kameya*

From the Department of Pathology,* Kitasato University School of Medicine, Kanagawa and the Department of Pathology, Saiseikai Central Hospital, Minato-ku, Tokyo, Japan

To elucidate the mechanism of tumor extension in human pulmonary adenocarcinoma, we immunohistochemically investigated the expression of cell cycle regulator proteins in 54 small adenocarcinomas less than 3 cm in diameter. The Ki-67-labeling index was significantly higher in the periphery of the tumor nodule than in the center. This proliferative potential correlated well with coexpression of cdk2 and cyclin A. p27, one of the cdk inhibitors, was highly expressed in normal bronchial epithelial cells. Peripherally located tumor cells expressed p27 at an intermediate level, but at a higher frequency and level than those in the center. Expression of p21 was also predominant in the periphery. Furthermore, the expression patterns of p21 and p27 were reciprocal. In vitro kinase assays further demonstrated higher cdk2 kinase activity in the periphery. These results suggest that: (i) within an emerging extension made up of peripherally located tumor cells, their high proliferative potential gradually wanes as their relative topographical position becomes more central in the expanding tumor; (ii) peripherally located tumor cells maintain their proliferative potential by higher cyclin A-cdk2 complex activity; and (iii) intermediate expression of p21/p27 in the peripherally located cells promotes higher cyclin A-cdk2 kinase activity, whereas high p21/p27 expression in nonneoplastic cells inhibits kinase activity.

This article has been cited by other articles:

				A. Psyrri, A. Bamias, Z. Yu, P. M. Weinberger, M. Kassar, S. Markakis, D. Kowalski, E. Efstathiou, R. L. Camp, D. L. Rimm, et al. Subcellular Localization and Protein Levels of Cyclin-Dependent Kinase Inhibitor p27 Independently Predict for Survival in Epithelial Ovarian Cancer Clin. Cancer Res., December 1, 2005; 11(23): 8384 - 8390. [Abstract] [Full Text] [PDF]

				T. Koga, S. Hashimoto, K. Sugio, I. Yoshino, S. Mojtahedzadeh, Y. Matsuo, Y. Yonemitsu, K. Sugimachi, and K. Sueishi Clinicopathological and Molecular Evidence Indicating the Independence of Bronchioloalveolar Components from Other Subtypes of Human Peripheral Lung Adenocarcinoma Clin. Cancer Res., June 1, 2001; 7(6): 1730 - 1738. [Abstract] [Full Text] [PDF]

				T. Noguchi, Y. Dobashi, H. Minehara, M. Itoman, and T. Kameya Involvement of Cyclins in Cell Proliferation and Their Clinical Implications in Soft Tissue Smooth Muscle Tumors Am. J. Pathol., June 1, 2000; 156(6): 2135 - 2147. [Abstract] [Full Text] [PDF]

				Y. Dobashi, M. Shoji, M. Kitagawa, T. Noguchi, and T. Kameya Simultaneous Suppression of cdc2 and cdk2 Activities Induces Neuronal Differentiation of PC12 Cells J. Biol. Chem., April 21, 2000; 275(17): 12572 - 12580. [Abstract] [Full Text] [PDF]

				K. Truong, M. Gerbault-Seureau, M.-N. Guilly, P. Vielh, G. Zalcman, A. Livartowski, A. Chapelier, M.-F. Poupon, B. Dutrillaux, and B. Malfoy Quantitative Fluorescence in Situ Hybridization in Lung Cancer as a Diagnostic Marker J. Mol. Diagn., November 1, 1999; 1(1): 33 - 37. [Abstract] [Full Text]