Dataset Information

Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness.

ABSTRACT:

Background

KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

Methods

We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer.

Results

KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility.

Conclusions

Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it may represent a novel target for biomarker development and a novel therapeutic target for breast cancer.

SUBMITTER: Jami MS

PROVIDER: S-EPMC4007601 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness.

Jami Mohammad-Saeid MS Hou Jinxuan J Liu Miao M Varney Michelle L ML Hassan Hesham H Dong Jixin J Geng Liying L Wang Jing J Yu Fang F Huang Xin X Peng Hong H Fu Kai K Li Yan Y Singh Rakesh K RK Ding Shi-Jian SJ

BMC cancer 20140315

<h4>Background</h4>KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.<h4>Methods</h4>We validated the previous microarray observation by tissue mic ...[more]

PMID: 24628760

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Dataset Information

Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness.

Background

Methods

Results

Conclusions

Publications

Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness.

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