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Tumor Biology

Abstract 5150: Identification of higher mRNA expression of both Kitenin and ErbB4 CYT-2 isoform as a molecular marker for the prediction of transition from colon adenoma to carcinoma

Jeong A Bae, Eun Gene Sun, Yoo-Seung Ko, Hui Jeong Choi, Woo-Kyun Bae, Sang-Hee Cho, Ik Joo Chung, Kyung-Sub Moon, Young-Hyun Yu, Hyung-Ho Ha, Hangun Kim and Kyung Keun Kim
Jeong A Bae
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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Eun Gene Sun
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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Yoo-Seung Ko
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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Hui Jeong Choi
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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Woo-Kyun Bae
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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Sang-Hee Cho
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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Ik Joo Chung
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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Kyung-Sub Moon
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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Young-Hyun Yu
Sunchon Natl Univ. Coll Pharmacy, Sunchon, Republic of Korea.
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Hyung-Ho Ha
Sunchon Natl Univ. Coll Pharmacy, Sunchon, Republic of Korea.
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Hangun Kim
Sunchon Natl Univ. Coll Pharmacy, Sunchon, Republic of Korea.
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Kyung Keun Kim
Chonnam National Univ. Med. School, Kwangju, Republic of Korea;
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DOI: 10.1158/1538-7445.AM2016-5150 Published July 2016
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Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA

Abstract

Purpose: The molecular events in the malignant progression of colon adenoma after loss of adenomatous polyposis coli (APC) are not fully understood. KITENIN (KAI1 C-terminal interacting tetraspanin) increases the invasiveness of colorectal cancer (CRC) cells and we recently identified a novel EGFR-independent oncogenic signal of EGF that works under co-expressed KITENIN and ErbB4. Here we tested whether elevated KITENIN and ErbB4 contributes to further progression of intestinal adenoma following APC loss.

Results & Discussion: The intestinal tissues of villin-KITENIN transgenic mice in which villin-driven elevated KITENIN induced increased c-Jun expression exhibit mild epithelial cell proliferation but no epithelial lineage changes, compared with those of non-transgenic mice. Among the 4 ErbB4 isoforms, JM-a/CYT-2 and JM-b/CYT-2 exhibited the highest AP-1 activity when cells co-expressing KITENIN and each isoform were stimulated by EGF. Interestingly, predominant overexpression of ErbB4 CYT-2 isoform mRNA as well as increased EGFR expression were observed in intestinal adenoma of APCmin/+ mice making the microenvironment of activated EGF signaling. When we crossed villin-KITENIN mice with APCmin/+ mice, intestinal tumor tissues in the crossed mice showed the characteristics of early stage invading adenocarcinoma. In CRC patients, ErbB4-CYT-2 mRNA expression was significantly greater in tumor tissues than in normal adjacent tissues, but no differences in tumoral expression between the stages, and a positive correlation exists between KITENIN and ErbB4-CYT-2 mRNA expression. Thus, elevated expression of KITENIN and ErbB4-CYT-2 is newly identified as a factor that promotes the transition of colon adenoma to adenocarcinoma within an APC-loss-associated tumor microenvironment.

Conclusion: Higher mRNA expression of both KITENIN and ErbB4-CYT-2 in colon adenoma tissues can be used as a molecular marker of the possible development of malignant transformation.

Citation Format: Jeong A Bae, Eun Gene Sun, Yoo-Seung Ko, Hui Jeong Choi, Woo-Kyun Bae, Sang-Hee Cho, Ik Joo Chung, Kyung-Sub Moon, Young-Hyun Yu, Hyung-Ho Ha, Hangun Kim, Kyung Keun Kim. Identification of higher mRNA expression of both Kitenin and ErbB4 CYT-2 isoform as a molecular marker for the prediction of transition from colon adenoma to carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5150.

  • ©2016 American Association for Cancer Research.
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Cancer Research: 76 (14 Supplement)
July 2016
Volume 76, Issue 14 Supplement
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Abstract 5150: Identification of higher mRNA expression of both Kitenin and ErbB4 CYT-2 isoform as a molecular marker for the prediction of transition from colon adenoma to carcinoma
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Abstract 5150: Identification of higher mRNA expression of both Kitenin and ErbB4 CYT-2 isoform as a molecular marker for the prediction of transition from colon adenoma to carcinoma
Jeong A Bae, Eun Gene Sun, Yoo-Seung Ko, Hui Jeong Choi, Woo-Kyun Bae, Sang-Hee Cho, Ik Joo Chung, Kyung-Sub Moon, Young-Hyun Yu, Hyung-Ho Ha, Hangun Kim and Kyung Keun Kim
Cancer Res July 15 2016 (76) (14 Supplement) 5150; DOI: 10.1158/1538-7445.AM2016-5150

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Abstract 5150: Identification of higher mRNA expression of both Kitenin and ErbB4 CYT-2 isoform as a molecular marker for the prediction of transition from colon adenoma to carcinoma
Jeong A Bae, Eun Gene Sun, Yoo-Seung Ko, Hui Jeong Choi, Woo-Kyun Bae, Sang-Hee Cho, Ik Joo Chung, Kyung-Sub Moon, Young-Hyun Yu, Hyung-Ho Ha, Hangun Kim and Kyung Keun Kim
Cancer Res July 15 2016 (76) (14 Supplement) 5150; DOI: 10.1158/1538-7445.AM2016-5150
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