23541

SEC14L2

C22orf6|SPF|TAP|TAP1;SEC14-like 2 (S. cerevisiae);SEC14L2;SEC14-like 2 (S. cerevisiae)

SEC14-like protein 2|alpha-tocopherol-associated protein|squalene transfer protein|supernatant protein factor|tocopherol-associated protein

22q12.2

protein-coding

Epidemiologic studies suggested that vitamin E has a protective effect against prostate cancer. We showed here that tocopherol-associated protein (TAP), a vitamin E-binding protein, promoted vitamin E uptake and facilitated vitamin E antiproliferation effect in prostate cancer cells. Interestingly, without vitamin E treatment, overexpression of TAP in prostate cancer cells significantly suppressed cell growth; knockdown of endogenous TAP by TAP small interfering RNA (siRNA) in nonmalignant prostate HPr-1 cells increased cell growth. Further mechanism dissection studies suggested that the tumor suppressor function of TAP was via down-regulation of phosphoinositide 3-kinase (PI3K)/Akt signaling, but not by modulating cell cycle arrest or androgen receptor signaling. Immunoprecipitation results indicated that TAP inhibited the interaction of PI3K subunits, p110 with p85, and subsequently reduced Akt activity. Constitutively active Akt could negate the TAP-suppressive activity on prostate cancer cell growth. Moreover, stable transfection of TAP in LNCaP cells suppressed LNCaP tumor incidence and growth rate in nude mice. Furthermore, TAP mRNA and protein expression levels were significantly down-regulated in human prostate cancer tissue samples compared with benign prostate tissues as measured by reverse transcription-PCR, in situ hybridization, and immunohistochemistry. Together, our data suggest that TAP not only mediates vitamin E absorption to facilitate vitamin E antiproliferation effect in prostate cancer cells, but also functions like a tumor suppressor gene to control cancer cell viability through a non-vitamin E manner. Therefore, TAP may represent a new prognostic marker for prostate cancer progression.

We show that TAP/Sec14L2 had a high expression in normal/benign breast, prostate, and liver tissues as compared to lung, colon, and kidney. Its expression was downregulated in breast cancer cell lines shown by quantitative-PCR. Further, 57% of 141 human invasive breast carcinomas had no or markedly reduced TAP/Sec14L2 expression by immunohistochemical staining, and the rate increased to 80% in high grade invasive carcinomas (p < .01). This downregulation of TAP/Sec14L2 was also present in ductal carcinoma in situ (DCIS) associated with invasive carcinomas. These findings raise the possibility that TAP/Sec14L2 may serve as a tumor suppressor in breast carcinogenesis.