Pyruvate carboxylase (PC) is an anaplerotic enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate, which is crucial for replenishing tricarboxylic acid cycle intermediates when they are used for biosynthetic purposes. We examined the expression of PC by immunohistochemistry of paraffin-embedded breast tissue sections of 57 breast cancer patients with different stages of cancer progression. PC was expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. We also found statistical association between the levels of PC expression and tumor size and tumor stage (P < 0.05). The involvement of PC with these two parameters was further studied in four breast cancer cell lines with different metastatic potentials; i.e., MCF-7, SKBR3 (low metastasis), MDA-MB-435 (moderate metastasis) and MDA-MB-231 (high metastasis). The abundance of both PC mRNA and protein in MDA-MB-231 and MDA-MB-435 cells was 2-3-fold higher than that in MCF-7 and SKBR3 cells. siRNA-mediated knockdown of PC expression in MDA-MB-231 and MDA-MB-435 cells resulted in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of PC in MCF-7 cells resulted in a 2-fold increase in their proliferation rate, migration and invasion abilities. Taken together the above results suggest that anaplerosis via PC is important for breast cancer cells to support their growth and motility.

We present for the first time, to the best of our knowledge, the potential clinical implications of the combined assessment of ASMA fibroblasts and cytoplasmic HMGB1 in breast cancer.

Asian Pac J Cancer Prev, 15 (1), [423][424][425][426] IntroductionCervical cancer is the second most common malignancy in women worldwide after breast cancer (Ferlay et al.). In Thailand, its incidence was 17.7/100,000 of Thai female population during (Khunhaprema et al., 2012. Cervical cancer incidences and deaths have decreased since the implementation of widespread cervical cancer screening with cervical cytology and/or human papilloma virus (HPV) (Saslow et al., 2012). The knowledge of HPV has been advanced. However, the cervical cytology is still the mainstay of cervical cancer screening. Colposcopy is the next investigation step for abnormal cervical screening patients after the followings; a) two consecutive unsatisfactory cytology results; b) most cases of positive HPV testing; c) repeated atypical squamous cell of undetermined significance (ASC-US) cytology; d) low grade squamous intraepithelial lesion (LSIL) cytology; e) atypical squamous cell, cannot exclude high grade squamous intraepithelial lesion (ASC-H) cytology; f) high grade squamous intraepithelial lesion (HSIL) cytology; g) some types of glandular abnormality (Massad et al., 2013